Micro Final1 Flashcards
What was the first virus discovered?
Tobacco mosaic virus
What was the first animal virus isolated?
Foot and mouth disease virus, in 1898
What is a major structural categorization for viruses based on the outer layer of the virus?
Enveloped viruses (with a lipid bilayer) and non-enveloped viruses
Are GI viruses usually enveloped or non-enveloped?
Non-enveloped
Is HIV an enveloped or a non-enveloped virus?
Enveloped
How many genomic groups of viruses are there? How many are based on DNA? How many are based on RNA?
Six; two DNA; four RNA
Viral genomic groups IV and V are both based on single-stranded RNA. What is the distinction between them?
Polarity: whether the genome as it enters the cell is the right orientation for translation in the protein, or needs to create an antisense RNA template that will be translated
How is a virus grown in a laboratory if they are obligate parasites?
On a host cell culture
Can you directly visualize viruses on an agar plate?
No, you can only see signs of virus infection, like cytopathic effect, inclusion bodies or hemadsorption
How are viruses being visualized in this assay?
By the number of plaques of killed cells
What is the eclipse period of viral growth? What is the latent period?
Eclipse: when you have a low, undetectable level of the virus, because it is within cells but not yet replicating; Latent: when there is a detectable level of virus but it has not yet reached the level of the infectious dose
Routes of viral infection include: […], respiratory, transcutaneous, sexual, and contact with infectious bodily fluid.
Routes of viral infection include: oral/fecal, respiratory, transcutaneous, sexual, and contact with infectious bodily fluid.
Routes of viral infection include: oral/fecal, respiratory, […], sexual, and contact with infectious bodily fluid.
Routes of viral infection include: oral/fecal, respiratory, transcutaneous, sexual, and contact with infectious bodily fluid.
Routes of viral infection include: oral/fecal, respiratory, transcutaneous, sexual, and contact with infectious […].
Routes of viral infection include: oral/fecal, respiratory, transcutaneous, sexual, and contact with infectious bodily fluid.
What percent of human cancers are thought to have a viral etiology?
15%
What general disease have HTLV-1, HBV, HCV, HPV, HHV-8, and EBV all been linked to?
Cancer
Historically, what has been the most effective way of combatting viral illness?
Vaccines
What effect is used here to assess the presence of viruses on the right?
The cytopathic effect: damaged cells are visible on the right
What shows a positive result in a hemagglutination test?
The virus spreads over the surface of a drop of hematies, and spreads it over a well
Herpes viruses include: the Herpes […] viruses, the Varicella Zoster virus, Epstein-Barr virus, cytomegalovirus, and Human Herpes viruses.
Herpes viruses include: the Herpes Simplex viruses, the Varicella Zoster virus, Epstein-Barr virus, cytomegalovirus, and Human Herpes viruses.
Herpes viruses include: the Herpes Simplex viruses, the […] virus, Epstein-Barr virus, cytomegalovirus, and Human Herpes viruses.
Herpes viruses include: the Herpes Simplex viruses, the Varicella Zoster virus, Epstein-Barr virus, cytomegalovirus, and Human Herpes viruses.
Herpes viruses include: the Herpes Simplex viruses, the Varicella Zoster virus, […] virus, cytomegalovirus, and Human Herpes viruses.
Herpes viruses include: the Herpes Simplex viruses, the Varicella Zoster virus, Epstein-Barr virus, cytomegalovirus, and Human Herpes viruses.
Herpes viruses include: the Herpes Simplex viruses, the Varicella Zoster virus, Epstein-Barr virus, […], and Human Herpes viruses.
Herpes viruses include: the Herpes Simplex viruses, the Varicella Zoster virus, Epstein-Barr virus, cytomegalovirus, and Human Herpes viruses.
What is the genomic content and structure of herpes viruses?
Large, enveloped dsDNA viruses (group I)
What timecourse of infection is caused by herpes viruses?
Chronic and latent infection
Where is the Herpes virus assembled during replication?
In the ER and Golgi
What is the mechanism of acyclovir? What class of viruses does it inhibit?
First it is phosphorylated by a viral thymidine kinase, and then when it is incorporated into the replicating DNA chain, replication is terminated
How do HSV I and II enter the body?
Abraded skin or mucosa
Where do HSV I and II lie latent after primary infection?
Sensory ganglia
What histological diagnosis is possible from this slide?
This is a giant cell with intranuclear inclusions (Tzanck test), indicating a herpesvirus infection
What is the prevalence of HSV-1 in adults? What is the prevalence of HSV-2?
50-70% for HSV-1; 20-50% for HSV-2
What is the appearance of herpetic lesions?
Crops of painful small blisters and ulcers in skin and mucous membranes
What is a herpetic infection of the finger called?
Herpetic Whitlow
What viral infection depicted here can cause painful swallowing?
HSV esophagitis
Besides the skin and mucous membranes, what are other common targets for HSV infection?
Conjunctiva, encephalitis, esophagus
What are presenting symptoms for a neonatal CNS infection by HSV?
Seizures, lethargy, irritability, fever with an onset at 14-21 days
Can HSV be cultured from CSF for a CNS infection? What lab technique is most appropriate for finding HSV in CSF?
No; PCR is more appropriate
Besides culturing and Tzanck smear, what other lab findings can be used to diagnose HSV?
Direct fluorescence antibodies of skin lesions and PCR of CSF
Is acyclovir available in IV form? What is the typical oral formulation?
Yes, IV acyclovir is used for serious disease; valacyclovir is the oral formulation, a prodrug that is better absorbed than acyclovir
How is resistance to acyclovir generated? Are they seen in typical patients?
Mutations in the viral thymidine kinase, or the DNA polymerase; no, resistance is mostly seen in immunocompromised patients
What can be used to treat acyclovir resistant HSV? What are its side effects?
Foscarnet, an inorganic pyrophosphate that inhibits the viral DNA polymerase; nephrotoxicity and calcium/phosphate dysregulation
What is Foscarnet used to treat? Does it have an oral formulation?
Acyclovir resistant HSV; no
What can be used to prevent HSV transmission from a pregnant woman with genital lesions to her infant?
C-section
In what cases might long term acyclovir be administered?
Pregnant women at risk of transmitting to their infant; transplant recipients; AIDS patients
What skin condition is seen here? What virus causes it?
Chicken pox; varicella zoster virus
What is the most contagious mode of transmission for varicella zoster virus?
Aerosolization from the respiratory tract
What is the time period of chicken pox infection? Which period is the contagious period?
2-3 weeks; 9-21 days
Where does the varicella zoster virus establish latency after an episode of chicken pox? If it reactivates, what does it cause?
Dorsal root ganglia; shingles
What percentage of shingles patients can recall that they were exposed to the virus in the past (e.g., had chickenpox)?
>90%
Can shingles be spread by respiratory droplets?
No, only during an initial exposure via the respiratory tract will the varicella virus be contagious via aerosolization, during shingles the latent virus in the dorsal root ganglia is reactivated
Do adults have more or less symptomatic reactions to varicella infection?
More symptomatic
What is a significant adverse neurological outcome for herpes zoster (shingles)?
Post-herpetic neuralgia, where pain or lack of sensitivity manifests in a nerve affected by the virus
How is shingles treated?
Acyclovir and valacyclovir, at higher doses than for HSV
Parainfluenza, coronavirus, and adenovirus are all viruses that affect which system?
Respiratory
What family of viruses do parainfluza viruses belong to?
Paramyxoviridae
Which family of viruses do respiratory syncytial virus and metapneumovirus belong to?
Pneumoviruses
What is the genomic makeup of a paramyxovirus?
Negative-sense, single stranded RNA
What is transcribed from the negative sense RNA paramyxovirus genome?
Individual mRNAs and a full length positive-sense RNA template
What is the “barking cough” a sign of? What is the typical infectious agent?
Croup, or laryngotracheitis; parainfluenza virus
Which HPIV viruses cause croup?
HPIV-1, -2, and -3
What is the steeple sign?
An anatomical hallmark of croup, which is the narrowing of the trachea in the subglottic region
What is the course of treatment for parainfluenza virus?
Usually supportive: IV/IM/oral dexamethasone, and nebulized racemic epinephrine
What is the clinical syndrome caused by RSV virus?
Bronchiolitis or pneumonia
Does the immune response to RSV appear to play a role in the pathogenesis and severity of bronchiolitis?
Yes
When are the usual seasons for RSV virus infection in temperate climates?
Winter and early spring
What treatment can be used for severe infections by RSV? What is its mechanism?
Ribavarin; nucleoside analog that inhibits nucleic acid synthesis
What antibody is used to prevent RSV infection in high risk infants? How often is it adminstered and via which route?
Palivizumab; monthly, IM
What virus is the 2nd leading cause of bronchiolitis after RSV? What percentage of common colds in children is caused by it?
Human metapneumovirus; 15%
Can human metapneumovirus and RSV be transmitted by close contact? In a nosocomial setting?
Yes to both
How is human metapneumovirus treated?
Supportive
What is the structure and genomic makeup of coronavirus?
Enveloped, single stranded, and positive sense RNA virus
Does paramyxovirus have a lipid envelope?
Yes
Where does the coronavirus assemble?
The rough endoplasmic reticulum
Besides the common cold, what can coronavirus manifest as clinically?
Gastroenteritis and SARS (Severe Acute Respiratory Syndrome)
What are the hallmarks of SARS? What is the mortality rate?
Fever, pneumonia/respiratory distress, diarrhea, and leukopenia; 10% out of 8000 infected individuals
What is the reservoir for coronavirus?
Common in many animals
How can coronavirus be diagnosed? When would these tests be needed?
PCR on respiratory secretions or stool, or EM; if SARS caused by coronavirus is suspected
Is there a proven effective antiviral therapy for coronavirus?
No
Are DNA viruses generally more or less complex than RNA viruses?
DNA viruses are more complex
What is the structure and genomic makeup of adenovirus?
Non-enveloped icosadeltahedral virus with linear, dsDNA genome
What membrane protein does adenovirus co-opt to enter the cell?
Integrin
Is the DNA genome of adenovirus delivered to the nucleus?
Yes
Does adenovirus replication lead to cell lysis?
Yes
What sort of patients can be suspected for adenovirus?
Young (<10yo) patients with pink-eye, sore throat, or fever and generalized rash
What patient populations are likely to have severe infections of adenovirus manifest (e.g. pneumonia, meningitis, and encephalitis)?
Young infants and the immunocompromised
What virus can cause all of these syndromes?
– URI/LRI
– Pharyngo-conjunctivitis
– Gastroenteritis
– Hemorrhagic cystitis
Adenovirus
How is adenovirus spread?
Aerosol, close contact, or fecal-oral
What is the typical first site of infection for adenovirus spread by aerosol?
Pharyngeal infection
Which cell type is infected by adenovirus in the respiratory and GI tract?
Mucoepithelial cells
Can adenovirus spread to visceral organs? In which tissue can it persist longest?
Yes; lymphoid tissue
What drug can be used to treat severe cases of adenovirus, e.g. in the immunocompromised? What is the mechanism? What toxicity results?
Cidofovir; it is a cytosine analog that blocks viral DNA synthesis; nephrotoxicity
What is the most frequent cause of the common cold?
Rhinovirus
What is the major vector for transmission of rhinovirus?
Hands
Does measles infect immune cells, epithelial cells, or both?
Both
What virus causes measles and from what family? What is its genomic structure? Is it enveloped?
Morbillivirus, from paramyxovirus family; negative strand nonsegmented RNA; enveloped
What are the three proteins in the envelop of the measles virus?
Hemagglutinin (H), fusion (F) and matrix (M)
Which protein on morbillivirus mediates fusion between the viral envelope and the host cell?
F protein
Which two proteins in morbillivirus drive RNA-dependent RNA polymerization? Where does this occur in the host cell?
L and P; in the cytoplasm
What receptor is used by morbillivirus to target epithelial cells?
Nectin 4, an epithelial cell receptor
What is the route of spread of measles?
Respiratory droplets
What is the latent period for measles? What symptoms characterize the prodrome?
10-14 days; 2-3 day prodrome of fever, coryza (cold symptoms), cough, and conjunctivitis
What visible sign of measles infection correlates with the initiation of viral clearance?
Maculopapular rash
What are the first cell types to be invaded by morbillivirus?
Macrophages and dendritic cells of the respiratory tract
What happens when the morbillivirus replicates in lymphoid tissue?
Formation of multinucleated giant cells as the envelope fusion proteins exert effects on the cell membrane, or “syncytium”
What initiates viremia from a measles infection?
Amplication of the virus in lymph nodes
Which cell in the blood is infected by the morbillivirus?
Lymphocyte
What is the average infection spread caused by one measles patient?
1 will infect ~10 without isolation
What viral infection is characterized by this rash?
Measles: it is a maculopapular, semi-confluent rash
What day of infection does the characteristic measles rash manifest?
~13 days
What bacterial complication is common in 5-15% of measles cases?
Superinfection involving otitis media, mastoiditis, sinusitis, etc.
What rare neurological disease beginning 2-10 years after infection is associated with measles?
Subacute sclerosing panencephalitis
What infection can cause a rare neurological disorder characterized by personality changes, intellectual deterioration, and possibly death about 2-10 years afterward?
Measles
How is measles diagnosed—clinically, or by lab tests?
Usually clinically (in atypical cases, measles antigen can be visualized with direct fluorescent antibody)
When does production of IgG begin after exposure to morbillivirus?
Around ~20 days afterward
How long can maternal antibodies suppress morbillivirus infection?
6 months
What is the treatment for measles?
None is available, so supportive
What kind of vaccine is the measles vaccine? What combination vaccine is it given with?
Live attenuated virus; measles mumps and rubella (MMR)
When are the MMR vaccines administered to children?
Between 12-15 months with a booster at 4-6 years
When was the measles vaccine introduced in the US?
1963
What is the reason for sporadic outbreaks of measles in select populations of the US?
Refusal of vaccination
Where is measles still common?
Africa and Asia
What viral infection is characterized by this presentation?
Mumps (from the british to “mump”, which means to grimace or grin)
Which gland swells in the presentation of rubulavirus (which causes mumps)?
The parotid gland
Which virus causes mumps, and what family does it belong to?
Rubulavirus, from the paramyxovirus family
On what day of infection does mumps spread to the spleen and lymphoid tissue?
7-10 days
What fraction of mumps cases results in meningitis?
10%
What fraction of mumps cases are subclinical?
30%
What is the type of vaccine used for mumps? What vaccine is it included with?
Live attenuated virus; MMR
What disease causes this rash?
Rubella
What is the genomic makeup of the rubella virus? What family does it belong to? Does it have an envelope?
Positive strand RNA virus; Togavirus; enveloped
What happens if a pregnant mother is infected with rubella in the early months of pregnancy?
Congenital rubella syndrome, which causes birth defects such as deafness, cataracts, heart defects, and mental retardation (>20% chance)
What is the type of vaccine used to counter rubella?
Live attenuated virus
What kind of drug is azidothymidine (AZT)?
A nucleoside reverse transcription inhibitor (NRTI), used to treat HIV by blocking the reverse transcriptase
Which class of HIV drugs is most similar in mechanism to acyclovir?
Nucleoside reverse transcriptase inhibitors: molecules that are similar to nucleosides, are incorporated into the chain by viral reverse transcriptase and terminate transcription
What are two major adverse effects of NRTIs as a class of drugs?
Mitochondrial toxicity (muscle weakness, mental status changes, pancreatitis, lactic acidosis) and dyslipidemia
What is the common name for azidothymidine?
Zidovudine
Which NRTIs have minimal toxicity outside of the mitochondrial toxicity and dyslipidemia caused by all NRTIs?
Lamivudine (3TC) and emtricitabine (FTC)
Which NRTI can cause a hypersensitivity reaction in certain HLA genotypes?
Abacavir (ABC)
Which NRTI has a high probability of renal toxicity or osteopenia?
Tenofovir (TDF)
Which two NRTIs have a particularly high risk of mitochondrial toxicity and insulin resistance?
Didanosine (ddI) and stavudine (d4T)
When did the era of combination anti-retroviral therapy for HIV begin?
1995-6
Does resistance develop faster with NRTIs or NNRTIs?
Generally, NNRTIs
What class of drugs do nevirapine, efavirenz, etravirine, and riplivirine belong to?
Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
What adverse effect is common to efavirenz, etravirine, and rilpivirine?
Rash
Which NNRTI can cause a hypersensitivity reaction that is more common in women and in patients with high CD4+ cell counts?
Nevirapine (NVP)
How do NNRTIs inhibit viral reverse transcriptase?
Binding to an outside allosteric pocket: they do not target the active site of DNA synthesis directly
What liver enzyme is affected by NNRTIs that crease toxicity across the entire class of drugs?
Cytochrome P450
What class of drugs do atazanvir, darunavir, fosamprenavir, and lopinavir/ritonavir belong to? What infection are they a first-line agent for, assuming the infectious agent has not been exposed to drugs previously?
Protease inhibitors; HIV
Can ritonavir be used for its antiretroviral effect?
No, it is a potent CP450 inhibitor, it is only used as a pharmacokinetics booster at a low dose (since it allows another drug, e.g. lopinavir, to maintain effective plasma concentrations for longer)
What are adverse effects of all protease inhibitors?
Dyslipidemia, lipohypertrophy, and cytochrome P450 interactions
What class of drugs do nelfinavir, indinavir, and saquinavir all belong to? What are they used to treat?
Protease inhibitors; HIV
Do we still use the “treat early, treat hard” mantra for HIV?
No, treatment is now based on CD4+ counts, VL, and symptoms
By how much has mortality decreased for HIV in the US since the introduction of protease inhibitors and NNRTIs?
42%
What class of drugs do raltegravir and elvitegravir belong to? What is their function?
Integrase strand transfer inhibitors; they inhibit the enzyme that integrates the HIV genome into the host cell
What CCR5 antagonist is used to treat HIV? Does it work on all strains of the virus?
Maraviroc; no, it requires the CCR5 tropic virus
What happens during periods when HIV patients are not taking their medications properly?
Populations of drug resistant virus will replicate and re-infect cells, leading to a potentially very resistant infection
Can a sample of HIV from a patient be measured for resistance to various antiretrovirals?
Yes
What is being performed by this kind of assay?
Phenotypic resistance testing on a patient’s strain of a virus
What kind of prophylaxis is common for opportunistic infections of Pneumocystis jiroveci and Mycobacterium avium-complex in HIV patients?
TMP-SMX for P. jiroveci and Azithromycin for M. avium-complex
What percentage of HIV infected people in the US are estimated to be diagnosed? How many are retained in active HIV care?
80% diagnosed; 40% receiving ongoing care
Can antiretroviral therapy be given to prevent mother to infant transmission of HIV or infection post-exposure to contaminated fluids?
Yes
Does an efficacious AIDS vaccine currently exist? When was the last clinical trial for them performed?
No; 2012 ALVAC/AIDSVAX trial in Thailand
Has the number of people infected with HIV declined or increased since 1996? Are deaths stable, rising, or decreasing?
Infections have declined; deaths are decreasing slightly
What is the current first-line regimen for HIV?
Tenofovir and emtricitabine (NNRTIs) with either efavirenz (NNRTI), darunavir+ritonavir (PI), atazanavir+ritonavir (PI), or raltegravir (INSTI)
Which class of MHCs is responsible for presenting viral peptides?
MHC class I
Which kind of cells participate in cell mediated immunity against viruses?
Cytotoxic T-cells specific for immunogenic viral peptides
What cell types are involved in the humoral immunity response to a virus?
Helper (CD4+) T cells and B cells
What type of vaccines are the MMR and VZV vaccines?
Live-attenuated virus vaccines
When was the last case of paralytic poliomyelitis in the US?
1999
What are the current flu vaccines composed of? What phenomenon is responsible for the need for a new vaccine every year?
Two prevalent strains of influenza A (one H1N1 and one H3N2) and the single most prevalent strain of influenza B from the past year; antigenic drift requires updating of the vaccine
How many deaths are still attributable to measles worldwide per year?
~140k
Why can’t the Rubella vaccine be given during pregnancy?
Concerns for congenital rubella
Is the mumps vaccine 100% effective?
Some recent cases of mumps have occurred in vaccinees
What is an adverse effect of the varicella vaccine?
It may occasionally produce mild vaccine-associated disease
What is the difference between Varivax and Zostivax?
Zostivax is a zoster vaccine (same virus as varivax) but at a 10x higher dose intended for ≥60 yo patients
Should live virus vaccines be given to patients with defective cell-mediated immunity?
No, because they could contract the disease
What is the composition of the human papillomavirus vaccine? Does it contain nucleic acids
Reassambed virus-like particles; no
How is HPV typically transmitted
By direct (sexual) contact
What are common adverse reactions to viral vaccines?
Fever, injection site reactions and a mild rash after MMR
What was a risk of the live oral vaccine for polio? What change in the polio vaccine was introduced to prevent it?
Small chance of developing paralytic polio; an inactivated whole virus viaccine is now used
What would be a contraindication to administering any vaccine?
A prior anaphylactic reation
What allergy is checked before administering the influenza vaccine?
Eggs, since the vaccine is cultured in eggs
What happened to the paper published in the Lancet by Wakefield et al. claiming vaccines could cause autism?
It was retracted 10 years later
What are the top three cancers attributable to HPV?
Cervix, oral cavity and larynx
Which type of cancer caused by HPV represents 10% of female cancers worldwide?
Cervical cancer
Is HPV infection common or rare? How many types or strains are there?
Very common; >140 types/strains
What are the symptoms of infection with a low-risk HPV type?
Ano-genital condyloma (genital wart) and low-grade dysplasia
Which are the HPV types that are most prevalently associated with high grade dysplasia and cervical cancer?
16 and 18
What proportion of cervical cancers are associated with HPV infections?
>99%
What proportion of anal, vaginal, and penile cancers are attributable to high-risk HPV infection?
70-85% of anal cancers and 40-50% of vaginal and penile cancers
What is the outcome for most HPV infections?
Spontaneous clearance
What are suspected coexisting risk factors for cervical cancer post HPV infection?
Smoking, host polymorphisms, oral contraception, and other STDs
What is the structure and genomic makeup of HPV?
Non-enveloped dsDNA virus with a circular genome (7.9kbp)
Why are HPV proteins named either by E or L?
E is the early region of the genome that codes for replication proteins and oncogenic proteins, and L is the late region that codes for capsid proteins
Are keratinocytes easier or harder for cytotoxic lymphocytes to kill than most other cell types? How does this affect HPV infection?
Harder; HPV can survive more easily
Does HPV infect the bloodstream?
No
Both commercial vaccines for HPV contain VLPs. What are they?
Virus-like particles, or “shells” of the virus without the nucleic acid portion
HPV vaccines contain adjuvants. What is their purpose?
To stimulate a stronger immune response
What are the commercial names for the HPV vaccines?
Gardasil and Cervarix
Which HPV strains are covered by the HPV4 or quadrivalent (Gardasil) vaccine? Which are covered by the HPV2 or bivalent (Cervarix) vaccine?
Quadrivalent: 6,11,16,18;
Bivalent: 16,18
Is there a correlation between states with higher HPV vaccine uptake and lower cervical cancer rates?
Yes
When should HPV vaccines be first administered?
Boys and girls ~11-12 yo, before onset of sexual activity
Where do most anal cancers related to HPV infection develop?
The anal T-zone, where there is a transition from stratified squamous to columnar epithelium similar to the cervical T-zone
How many new infecitons of HPV occur per year in the US?
6.2 million
Do ACIP recommendations for the HPV vaccine address patients with a history of cervical dysplasia?
No, only women with a positive HPV screen or genital warts
Do people necessarily develop antibodies after HPV infection? Would thise cause serology studies to underestimate or overestimate the prevalance of infection?
No, less than 70% of people develop antibodies to an HPV type after infection; this causes underestimation of prevalence
What does aseptic meningitis means?
CSF is cultured and no bacteria grows, but the WBC count is elevated
What family of viruses do enteroviruses, rhinoviruses, and Hep A belong to?
Picornaviruses, small RNA viruses
How many enteroviruses are there?
At least 71 serotypes
Are enteroviruses seasonal?
Yes, summer and fall
Between May and September, what is the most common viral etiology of aseptic CNS infection?
Enterovirus
Can enterovirus survive in harsh environments?
Yes it can survive in sewage, the GI tract, and detergents
How does enterovirus conceal its receptor binding sites from antibodies?
They are contained within canyons formed by VP1
Is enterovirus cytolytic? What is its effect on host cell RNA synthesis?
Yes; it inhibits host cell RNA synthesis
How does Poliovirus enter the CNS?
It travels via motor neurons from muscle to the brain
How do echovirus, Coxsackie virus, Hep A, and poliovirus enter the body? How do they get to the target tissue?
Via the oropharynx; after entering the bloodstream
What is the mechanism of tissue injury of enteroviruses?
Cytolysis, except for Hep A, which is immune mediated
What two antibody types combat enterovirus infection?
IgA inhibits establishment of initial infection, while serum IgG prevents and controls viremia
What countries are still endemic for polio?
Afghanistan, Nigeria, and Pakistan
In what percentage of polio infections does paralytic disease result?
2%
Are asymptomatic polio carriers able to transmit the disease?
Yes, they can shed it in the stool and nasal secretions
What is the difference between the Salk and the Sabin vaccines? Which has a very low risk of causing an infection? What is that vaccine’s advantage?
Salk’s vaccine is inactivated, while Sabin’s is attenuated; Sabin’s has the potential to cause infection; Sabin’s is easier to administer (it can be given orally)
Is the Sabin vaccine for polio used in the US?
No, the inactivated Salk vaccine is used
What class of virus related to Hep A can cause these symptoms?
Enteroviruses
What condition is this, and which virus causes it?
Herpangina caused by Coxsackie A
What disease is this and what virus causes it?
Hand, foot, and mouth disease caused by Coxsackie A
What are possible manifestations of Coxsackie B virus?
Pleurodynia, myocarditis, pericarditis, and overwhelming neonatal disease
What enterovirus besides Coxsackie B can cause overwhelming neonatal disease?
Echovirus
What is the glucose and level in typical viral meningitis? What would they more likely be in bacterial meningitis?
Both are normal viral; they tend to be low with bacterial meningitis
What is the treatment for viral meningitis?
Usually supportive
Why is CSF glucose usually lowered in bacterial meningitis?
The bacteria consumes the glucose in the CSF
What infectious agent causes mad cow disease?
Prions
What disease are these histological findings in brain tissue common for?
Prion disease (mad cow): on the left, amyloid plaques, on the right, vacuoles
What is the prognosis for prion disease?
It is uniformly fatal over a period of months
What is the structure of a prion?
It is an infectious protein that lacks nucleic acid or a virus like structure
How do prions cause disease within brain tissue?
They are a conformational isomer of a normal host protein that seems to trigger a conformational change in the normal host protein, which spreads this misformed conformation to other instances of the protein
What human diseases (not transmitted by animals) are caused by prions?
Kuru disease, Creutzfeldt-Jacob disease (CJD) mostly in older patients, and variant CJD which can manifest at a younger age
What is the full name for Mad Cow disease?
Bovine spongiform encephalopathy
What led to this decline in mad cow disease seen in the UK?
Regulations on feeding cows animal products (e.g., the brains of other cows)
How long can infected individuals shed enteroviruses in the stool?
Weeks
How common are prion diseases?
Not at all
What is the most common viral cause of severe diarrhea in young children?
Rotavirus
What is the distribution of rotaviruses? How many children are infected by age five?
Worldwide; almost all
What is the percentage of childhood gastroenteritis hospitalizations that is attributable to rotavirus in first world infants? Is mortality common?
34%-52%; no
Which is the most common cause of gastroenteritis: rotavirus, adenovirus or bacteria?
Rotavirus
What are presenting symptoms for rotavirus?
Fever, vomiting, watery diarrhea, and dehydration
Are subsequent infections of rotavirus more severe or less severe?
Less severe
What is the transmission route of rotavirus?
Fecal-oral
Can rotavirus be cell cultured?
Yes
What family does rotavirus belong to?
Reoviridae
Which serotype group of rotavirus is most important clinically?
Group A
Why was rotavirus named with rota-?
It appears like a wheel on EM
What is the genomic structure of rotavirus? Does it have an envelope?
It is a segmented dsRNA virus; no envelope
What are the outermost proteins of rotavirus, participating in cell attachment?
VP4, also called the P antigen
How many segments does the rotavirus have? How many proteins are produced by each segment?
11; about 1 protein per segment
Does the dsRNA genome of rotavirus get transcribed into DNA during the life cycle of the virus?
No, it is replicated using an RNA-dependent RNA polymerase
Which protein in rotavirus induces secretory diarrhea?
NSP4
What viral proteins to rotavirus are the basis for humoral immunity following the first infection?
VP4 and VP7 which are on the surface of the virus
How many serotypes of rotavirus are included in the RotaTeq vaccine? What is the route of administration? What is the most important contraindication?
5 serotypes; 3 liquid doses at 2, 4, and 6 months of age; cannot be given to immunodeficient infants
What can happen to the genome of rotavirus after coinfection?
Shuffling or reassortment of the genomic fragments
How many serotypes was RotaShield able to protect against? Is it still on the market?
4 serotypes; no, because it was linked to intussusception (invagination of the intestine)
What is the valency of the Rotarix vaccine? Is it still used in infants?
1 serotype of rotavirus; yes, and it provides some cross-protection against other serotypes
What concern was raised with the Rotateq vaccine after highly sensitive nucleic acid sequencing?
PCV-1 and PCV-2 (a porcine virus) sequences were found in it, but the FDA cleared it
Has the rotavirus vaccines been shown to reduce incidence of rotavirus infection in infants?
Yes
What is the most common cause of outbreaks (e.g. isolated clusters) of nonbacterial acute gastroenteritis?
Norovirus
Are noroviruses easily grown in culture?
No
What family does norovirus belong to? What is their genomic structure? Do they have an envelope?
Calciviridae; + sense, ssRNA genome; no envelope
What are presenting symptoms for norovirus infection?
Mild febrile illness of watery diarrhea and fever, with more severe illnesses of fever, vomiting, headache, and constitutional symptoms
What proportion of the population is susceptible to norovirus? What mutation do 20% of humans have that confers resistance?
About 45%; 20% of people are resistant do to a mutation in FUT2 that alters the carbohydrates found on epithelial cells
Is norovirus usually diagnosed in the clinical setting?
No, but it can be identified for epidemiological purposes
Besides norovirus and rotaviruses, what other viruses can cause GI illness?
Enteric adenoviruses and astroviruses
Are all cases of viral hepatitis symptomatic?
No
How many kinds of hepatitis viruses are known to exist currently? Which one depends on another virus to successfully infect a patient?
Four: Hep A, B, C, and E; Hepatitis δ virus (delta agent) relies on Hep B for infection
What virus was originally called hepatitis G? Why was it renamed?
GB virus-C; it does not appear to replicate primarily in the liver
Which hepatitis viruses cause insidious (as opposed to abrupt) infection? What is their incubation period?
Hepatitis B and C; 45-160 days
What family of virus does Hep A belong to?
Picorna virus
What family of viruses does Hep B belong to?
Hepadnavirus
What family of viruses does Hep C belong to?
Flavivirus
Between Hepatitis B and Hepatitis C, which one usually causes subclinical infections?
Hepatitis C
Can Hepatitis A produce a chronic infection?
No
Which hepatitis viruses are transmitted via sexual contact? What about perinatal transmission?
B, C, D and commonly transmitted sexually and from mother to child, but A and E can also be transmitted sexually depending on specific acts
Is there a therapy for Hepatitis A?
No
Is there a vaccine for Hepatitis B? What about Hepatitis C?
Yes for B; no for C
How many people are chronically infected with HBV worldwide? What about in the US?
350M worldwide; ~1M in the US
Are vaccines for Hep B given routinely to US children?
Yes, since 1991
What is the genomic structure of Hepatitis B? Is it enveloped?
Partially double-stranded DNA, circular; Enveloped
Which antigen is on the surface of HBV? What are collections of this antigen without viral proteins called?
HBsAg; subviral particles
What proportion of acute infections of HBV result in subclinical disease?
60-65%
Is death due to acute Hepatitis B virus infection common?
No
What are the two serological proteins that differentiate between acute and chronic hepatitis B infection?
HBsAg is eliminated in acute infection, but remains in the plasma for chronic infections—also, acute infection with HBV results in production of anti-HBsAg antibodies
If you have been vaccinated for HBV, how can you be serologically differentiated from somebody who resolved an acute HBV infection?
You will not have anti-HBc IgG, since your immune system was never exposed to HBc (the HBV core protein)
With acute and early acute HBV infection, which class of Ig to HBc is not yet present against HBc? What class of antibody for HBc develops during acute HBV infection?
IgG is not present during acute infection; IgM antibodies for HBc are released during acute HBV infection
Does chronic HBV infection increase the risk of liver cancer? Why or why not?
Yes; there are two theories, where either virus is activating oncogenes, or the chronic hepatic injury leads to genetic changes in hepatocytes that disrupts growth regulation
What are the two therapies available for HBV?
Pegylated interferon α and reverse transcriptase inhibitors
When would you treat for HBV as opposed to letting an acute infection running its course?
If the patient is positve for HBsAg for a long time (> 6mo), has a very high viral load, or evidence of liver disease (e.g. elevated ALT)
Are all the HBV antivirals available NRTIs or NNRTIs?
NRTIs (nucleoside analog reverse transcriptase inhibitor)
Which antiviral has HBV developed widespread resistance to?
Lamivudine
Which antiviral for HBV is the most expensive? Why is it used anyway?
Entecavir; because resistance has developed to the cheapest drug, lamivudine
Does Hepatitis δ virus infection alter the prognosis for HBV infection?
Yes, it increases the likelihood of death from fulminant hepatitis, and the chance of cirrhosis and hepatocellular carcinoma from chronic HBV
How many people in the US have a chronic HCV infection?
~3.2 million
What is the leading indication for liver transplants in the US?
Chronic HCV infection
What is the most common source of HCV infection?
IV drug use
What is the genomic structure of HCV? Is it enveloped?
It is a single stranded, positive sense RNA virus; yes it is enveloped
How many ORFs does HCV have? How can it produce more proteins than it has ORFs?
It has only one; polyprotein self-cleavage
What is significant about the evolutionary dynamics of HCV?
It has a high mutation rate do to an error-prone RNA polymerase, and therefore it can escape immune responses and interferon treatment
What is the most clinically significant genotype of HCV seen in the US?
Genotype 1
Which areas of the world do not have a prevalence for genotype 1 of HCV?
Central Africa and the Arabian peninsula have predominantly genotype 4; South Africa has predominantly genotype 6
What serological quantities differentiate between acute and chronic HCV infeiton?
Acute HCV infection has no HCV RNA detectable after several years, and ALT levels remain low, while chronic HCV infection results in spiky ALT levels and recurrently detectable HCV RNA
Acute:
Chronic:
What causes some individuals to retain latent HCV while it is cleared in others?
It is not entirely understood, but co-infection with HIV, evasion of immune responses, impaired NK or dendritic cells, or the glycosylated envelope are thought to play significant roles
How long does it take for antibodies to HCV proteins to be detected after exposure?
6-8 weeks
What is the standard of care for HCV?
Pegylated interferon, ribavarin and a protease inhibitor
How does a protease inhibitor contribute to the treatment regimen for HCV?
It prevents breakdown of the polyprotein into the 10 constituent proteins that make up the virus
Do all people respond to HCV therapy?
No, some have a sustained virologic response (success), but others have viral load drop to undetectable levels and still return later
Which genotype of HCV responds worst to interferon + ribavarin therapy? What variable can be adjusted to maximize that genotype’s response?
HCV genotype 1 responds most poorly; with a higher dose and longer treatment course, there is a greater chance of sustained virologic response
What are the two protease inhibitors used in HCV therapy?
Telaprevir and boceprevir
Which genotype of HCV are telaprevir and boceprevir approved to treat?
Genotype 1
How is hepatitis A virus transmitted? What is the usual timecourse of disease?
Fecal-oral; about 3 weeks
When is hepatitis A virus infection a risk for fulminant hepatic failure?
Previous infection with HBV or HCV
How many acute cases of hepatitis A are estimated to occur within the US each year?
<20k, as it has dropped since the licensing of the vaccine
During what week of hepatitis A infection might a spike in ALT levels be seen?
Between week 1 and week 2
Is Hepatitis E virus commonly found in the US?
No, it is predominantly in developing countries where fecal contamination of drinking water occurs
What is a risk factor for fulminant hepatitis in women that are infected with hepatitis E?
Pregnancy, with a mortality rate of 20% in the third trimester
Is Hepatitis B or Hepatitis C virus more genetically heterogenous?
Hepatitis C virus
Do patients with chronic HBV infection ever develop antibodies to the HBV S antigen?
No
How many people are estimated to have HIV in North America?
~1.5 million
How is the HIV genome integrated into the host cell genome if it is an RNA virus?
A RNA-dependant DNA polymerase (reverse transcriptase)
What is the evolutionary origin of HIV?
SIV, a simian virus that jumped to humans
Which group of HIV-1 causes the most human disease?
The M group
What are the two surface proteins on HIV involved in fusion?
gp41 and gp120
Does HIV have a lipid bilayer?
Yes
What is the genomic structure of HIV?
Double-stranded positive sense RNA
Is HIV enveloped?
Yes, by *env *proteins
What is the function of the LTR of the HIV genome?
Regulates transcription of the genome
Which gene product of HIV codes for matrix and capsid proteins?
Gag
Which gene product of HIV codes for the reverse transcriptase, protease, and integrase?
Pol
Which does regulatory or accessory genes are absolutely required for HIV infectivity? How many are there in total?
Tat and *Rev *are necessary; six in total
Which HIV protein attaches to CD4 and CCR5 or CXCR4 to initiate fusion into the T cell? What other viral protein mediates this?
gp120 attaches to the receptors; gp41 mediates it
What T cell mutation can produce resistance to HIV infection? What is the phenotype for heterozygous individuals?
A homozygous deletion of 32 basepairs in CCR5; heterozygous individuals can be infected but it progresses slowly
Why does HIV mutate so rapidly within the host?
The reverse transcriptase is very error prone, misreading a base every 2000 bases
What allows HIV to remain latent within T cells for years and constitutes a major barrier to curing HIV with small molecule therapies alone?
It is integrated into the host cell genome of T cells as a pro-virus
What feature of mRNA is used to produce many proteins from the small genome of HIV?
Alternate splicing
When immature polyproteins in HIV are cleaved by PR to generate infectious viral particles, where are the immature viral particles—intracellular or extracellular?
They have budded and so are extracellular
How do Vif and Vpu increase the virulence of HIV?
They block host cell proteins that counter viral replication
What is the transmission rate of HIV from mother to child in utero, at birth, or through breastfeeding without intervention?
25%
Does male to male transmission increase the risk of HIV transmission over other gender pairings? Do STIs increase the risk of HIV acquisition?
Yes to both
In a stratified epithelium (e.g. of the rectal or vaginal canals), how do viral particles get to T cells?
An abrasion allows presentation of particles to dendritic cells that migrate to T cells
Why is the rectal epithelium more susceptible to HIV transmission than the vaginal epithelium?
It is more susceptible to trauma, and vaginal secretions form a strong barrier to HIV transmission
Can HIV be found in the gut within days of infection? What about the CNS?
Yes to the gut, in its lymphoid tissues; yes it can also be found in the CNS
At approximately how many weeks following primary infection does HIV load drop to initiate the latent or chronic period?
9 weeks
What are the symptoms of acute HIV syndrome?
Similar to mononucleosis or flu-like illness: fever, sore throat, and malaise
What is the fastest lab test for determining acute HIV infection?
RNA PCR, which is faster than detecting antibodies
During latency, does HIV still replicate?
Yes, billions of viral particles are produced per day
If there is no viral load of HIV detectable in plasma, does that mean that an HIV patient has been cleared of the virus?
No, it is likely still in the lymph nodes
Why do CD4 T-cell counts drop following HIV infection?
The virus can kill cells or trigger apoptotic pathways, and infected cells are also killed by the immune system or experience anergy due to inappropriate signalling
Can an HIV patient have high IgG levels? Why or why not?
Yes, because they often are in a state of hyperactivation of T cells and B cells, which make more antibodies and cytokines
Does HIV cause direct neuronal damage?
Yes, possibly because of direct infection of microglia, or because shed gp120 activates microglia to produce neurotoxins
What is the main line of defense against HIV? Why can HIV evade them so easily?
Cytotoxic T lymphocytes; HIV infects CD4 T cells which would normally activate these lymphocytes, but cannot following infection
What three properties of the surface proteins of HIV make it hard for the immune system to develop a response?
They are glycosylated, making it difficult to develop antibodies against them. They mutate quickly. Conserved regions are recessed or hidden.
When the rate of loss of CD4 T cells increases steadily, what stage of HIV has been reached? What clinical symptoms are present?
AIDS; opportunistic infections begin to appear
When extracellular bacteria elicit an adaptive response, what effector mechanisms are used to rid the body of the bacteria?
Phagocytosis via opsonization by antibodies, concurrent with neutralization of the microbes and their toxins by the antibodies
How do superantigens like SEB trigger a hyperactive systemic inflammatory response?
They grip the TCR-HLA interaction and lock them together, causing uncontrolled hyperactivation of T cells and release of cytokines
What class of bacteria carry lipoteichoic acid? What serious inflammatory condition can it cause?
Gram positive; septic shock
What does S. epidermidis form to evade the immune system?
Biofilms
Why does S. aureus have coagulase?
It encourages clot formation, which allows immune evasion
Staphylococci are catalase positive. Why does this enzyme make them more virulent?
Catalase allows them to neutralize ROS released by immune cells attempting to kill them during phagocytosis
How are the number of intracellular bacteria controlled during the innate immunity phase of infection?
Macrophages release IL-12, which activates NK cells, killing infected macrophages
How are infected cells killed during the adaptive immunity phase of infection by intracellular bacteria?
CD4+ T helper cells activated by IFNγ from macrophages activate CD8+ cytotoxic T lymphocytes, which find the infected macrophages and kill them
If intracellular bacteria cannot be eliminated and chronically stimulate the immune system, what do lymphocytes form in response?
Granulomas
What is the first immune cell type to respond to a viral infection?
NK cells
What cytokine upregulates the cytotoxicity of NK cells?
Type 1 interferons
When an RNA virus has a segmented genome like influenza does, what can happen in a coinfected host?
The virus can swap segments producing a differently virulent strain
Which five steps of the Class I MHC pathway are obstructed by viruses to obscure the infected state of the cells they enter?
The proteasomes, the TAP transport, MHC synthesis, MHC survival in the ER, and CTL recognition of the MHC
Why might viruses produce cytokines or cytokine receptor decoys?
They may release cytokines that downregulate immune responses or decoy receptors to absorb inflammatory cytokines
What pathway is blocked by all infectious human viruses?
Type 1 interferon
What do dengue virus, yellow fever, West Nile, and hantaviruses have in common?
They are significant zoonotic viruses (transmitted by animals)
What does “arbovirus” mean?
Borned by arthropod, e.g., mosquitos
What virus family do denguevirus, West Nile, and yellow fever all belong to?
Flaviviridae
What is the genomic structure of flaviviridae?
Single stranded positive sense RNA
What prevents flaviviruses from generally causing viremia and then encephalitis?
Antibody block by the immune system
How do alpha and flavivurses enter the host cell?
Receptor-mediated endocytosis
Does denguevirus have an envelope?
Yes
How much of the world’s population is at risk for denguevirus infection?
About half
Which mosquito species transmits denguevirus?
- Aedes aegypti*
- *
How can the mosquito that spreads denguevirus be identified visually?
Aedes aegypti has white bands or scale patterns on its legs
Can the Aedes albopictus mosquito transmit denguevirus? Can humans transmit it to each other?
Yes, this mosquito can; no, humans do not transmit to each other
Can a patient be infected with multiple serotypes of denguevirus within a few weeks of exposure?
Typically no, because they provide short-term cross-immunity
What serious complications of denguevirus can occur during the second phase of illness?
Dengue hemorrhagic fever and dengue shock syndrome
Between the primary and secondary infection phases of denguevirus, is the virus detectable? What about IgG to denguevirus antigens?
The virus is not detectable, but IgG is
What proportion of denguevirus cases cause hospitalization?
10%
Is there a vaccine for denguevirus?
No, but three are undergoing trials
Does a treatment for denguevirus exist?
Not yet, but a novel antiviral is being developed
How can denguevirus be detected via laboratory testing?
Anti-DENV IgM in serum, or PCR
What is the most effective currently available method for denguevirus control in a population?
Controlling (eliminating) the vector, which is the mosquitos
Why are scientists introducing Wolbachia pipientis bacteria into A. aegypti mosquitos?
It is a benign bacterium for mosquitos but reduces the chance that they can carry denguevirus, and this strategy is being tried in Australia
What happened to the Sanofi Pasteur vaccine for dengue virus?
There was only 30% efficacy and no enhancement of immune response, hence it is being redesigned
What is the natural reservoir for yellow fever?
Monkeys
What vector is used by yellow fever virus to move from monkeys to humans (typically)?
Mosquitos
Is a vaccine available for yellow fever?
Yes, a live virus vaccine is available and mandatory in some YF affected countries
How do arboviruses enter the body in the course of eventually manifesting as encephalitis?
Via subcutaneous tissue (puncture wound, mosquito)
What is the seasonality of arborvirus-caused encephalitis? What other viral encephalitis tracks this seasonality?
Most common in late summer to early fall; Enterovirus
What is the genomic structure of West Nile virus? Is it enveloped?
Single stranded positive sense RNA; yes it is enveloped
Approximately how many cases of West Nile occur in New York State per year, based on 2009 data?
~6
Is an animal model for West Nile available?
Yes, in mice
What mutation confers resistance to HIV infection but increased risk for West Nile infection?
A deletion in CCR5
Can West Nile be spread by exposures other than the mosquito vector?
Yes, via transfusion, transplant, or mother → child via placenta or breast milk
Out of eastern equine encephalitis, western equine encephalitis, St. Louis, and La Crosse, which infection has the greatest mortality rate?
Eastern equine encephalitis
Where is Hantaanvirus endemic? What vector do they use? What is the presenting symptom?
Russia, China, and Korea; the striped field mouse; hemorrhagic fever with renal syndrome
What two types of hantavirus are significant in the US and Canada? What do both cause?
Sin Nombre and New York hantavirus; hantavirus pulmonary syndrome
How do hantaviruses infect a human host?
Via the pulmonary tract, upon inhalation of virus-contaminated aerosols of rodent excretions
What is the genomic structure of Rhabdoviruses? Is it enveloped? What is notable about the viral shape?
single-strand negative-sense RNA; yes; it is bullet-shaped
How many cases of rabies present per year in the US? How much is spent on rabies post-exposure prophylaxis?
2 cases per year; $300 million per year on prophylaxis, since many patients are bitten by animals
What cell types are infected and locations of replication for rhabdovirus?
Muscle and nerve cells
Does rabies cause neuronal necrosis?
No, but it still injures the CNS somehow
What infection characteristically produces Negri bodies in the brain?
Rhabdovirus (rabies)
What are presenting symptoms of rabies that has infected the CNS? How quickly can death occur?
Personality changes, parathesis, pain at the site of exposure, and other neurologic symptoms; 18 days after viral prodome
How can rabies be diagnosed?
Biopsy and immunofluorescence from skin on the nape of the neck, and PCR on CSF, saliva, and tissue
What are these indicated features in a pathology study of Rabies infection of the CNS?
Negri bodies
What family do Epstein-Barr virus and Cytomegaloviruses belong to?
Herpes viruses
What herpes viruses are latent, is there synthesis of viral particles?
No
What is the genomic makeup of all herpes viruses? Are they enveloped?
Large double stranded DNA viruses; yes, enveloped
What cell type does EBV infect and remain latent in?
B lymphocytes
What happens to life cycle of B cells infected by Epstein-Barr virus?
They become immortalized
What cancer can immunocompromised hosts of Epstein-Barr virus develop?
Lymphoma
Can the Monospot test be used in patients of all ages? What virus is it used to detect?
No, it is not sensitive in young children; Epstein-Barr
Which serological protein steadily rises and plateaus during convalescence of Epstein-Barr?
EBNA
What proportion of early childhood infections by Epstein-Barr are asymptomatic?
50%
What proportion of the US population is infected with Epstein-Barr by age 30?
70%
What virus causes infectious mononucleosis?
Epstein-Barr virus
What viral infection is consistent with fever, pharyngitis, lymphadenopathy, hepatosplenomegaly and rash that gets worse with ampicillin or amoxicillin?
Mononucleosis (Epstein-Barr)
How long does it take for infectious mononucleosis to resolve?
2-3 weeks
Which virus is associated with Burkitt’s, Hodgkin’s and CNS lymphoma in AIDS? What other cancer is associated with this virus?
Epstein-Barr virus; nasopharyngeal carcinoma
What is this condition? Is it malignant? What virus(es) is it associated with?
Oral hairy leukoplakia; it is non-malignant; Epstein-Barr in the context of HIV infection
What is the level of association between post-transplant lymphoproliferative disease and Epsteinn-Barr virus?
Very high (90%)
What serological protein level characterizes chronic active Epstein-Barr virus?
A lack of EBNA response and high titers of acute phase antibodies (EA and VCA)
How Epstein-Barr treated?
Supportively
Why might rituximab be given to somebody that previously had an Epstein-Barr virus infection?
It is used to treat certain EBV-related malignancies by controlling B cell proliferation
What is the mechanism of rituximab?
It is an antibody to CD20, a B-cell marker, which initiates antibody-dependent cellular cytotoxicity, complement activation, and apoptosis in malignant B cell lymphomas
What proportion of the young population is infected with CMV?
70-90%
What bodily fluids contain CMV?
Saliva, vaginal fluid, semen, and urine
How does cytomegalovirus downregulate the immune system?
It downregulates MHC I expression
What is the function of UL97 in cytomegalovirus and how does it relate to the drug Gancyclovir?
It is a viral kinase that phosphorylates Gancyclovir, a viral polymerase inhibitor
Is mononucleosis always caused by Epstein-Barr virus?
No, there is an EBV-negative mononucleosis that is usually milder and caused by cytomegalovirus (CMV)
What is the number one cause of congenital hearing loss in the US?
Cytomegalovirus infection
What is the most common patient population with cytomegalovirus seen in hospitals?
Immunocompromised patients
What are some complications of congenital cytomegalovirus infection?
Hepatitis, thrombocytopenia, CNS disease, retinitis, and hearing loss
How can CMV be diagnosed in newborns? Why is this technique less useful in an adult?
Urine culture; Infection and reactivation are so common in adults that such assays would not be specific or sensitive
What is the first line treatment for cytomegalovirus infection in a newborn or the immunocompromised? What is its mechanism?
Ganciclovir; it is a nucleoside analogue that inhibits the viral polymerase
What is the difference between ganciclovir and valganciclovir?
Valganciclovir is a better orally absorbed version of ganciclovir
What are cidofovir and foscarnet second line treatments for?
Cytomegalovirus infection
What are two second line treatments for CMV infection?
Cidofovir and foscarnet
What virus is this rash and timecourse typical of?
Roseola
Which virus causes roseola?
Human herpes virus 6 (HHV-6)
What is the genomic structure of cytomegalovirus? It is enveloped?
It is a double-stranded DNA virus; yes it is enveloped
What cell types are infected by HHV-6?
Lymphocytes, monocytes, and macrophages
What virus is most closely related to HHV-6 that infects nearly all children by age 5?
Human herpes virus 7 (HHV-7)
What is another name for HHV 8, which causes the following skin presentation?
Kaposi’s sarcoma associated herpesvirus
Which herpesvirus is not widely distributed in the population? Who does it infect?
HHV 8 or Kaposi’s sarcoma associated herpesvirus; immunocompromised
How is HHV-8 typically transmitted in the US?
Sexual contact (more often seen in MSM)
Are gastrointestinal symptoms possible with an influenza infection?
Yes, but they are rare
Besides pneumonia, what are three other serious complications of influenza?
Otitis media, Reye’s syndrome, and encephalitis
What happened in 1918 that caused life expectancy in the US to drop by more then 12 years?
The Spanish Flu epidemic
What is the most frequently isolated type of influenza? Which causes the most severe disease?
Type A for both
Which type of influenza has an animal reservoir?
Influenza type A
What are the black blobs within these EM images of influenza?
Individual RNA strands
How many different influenza A virus hemagglutin subtypes are there?
17
What does the H in e.g. H1N1 refer to?
Hemagglutinin subtype
What is the difference between antigenic drift and antigenic shift?
Drift is the change in the hemagglutinin from year to year, caused by point mutations, while shift is the occasional change that results from a reassortment event between human and avian influenza strains
What does the N in H1N1 stand for?
Neuraminidase
Which strain of influenza is more deadly once the case is discovered: swine H1N1 influenza, or avian H5N1 influenza?
Avian H5N1 is more deadly
What are the two classes of FDA-approved influenza antivirals? Which are approved against type B influenza?
Ion channel blockers and neuraminidase inhibitors; only the latter is effective against type B
What are two ion-channel blockers approved for use against influenza? Which type(s) of influenza can they treat?
Amantadine and rimantadine; only type A
What are two neuraminidase inhibitors approved for use against influenza? Which type(s) of influenza can they treat?
Zanamivir and oseltamivir; both A and B type influenza
Which ion channel on influenza is blocked by amantadine?
M2
Which stage of influenza replication is inhibited by ion channel inhibitors? Which stage is inhibited by neuraminidase inhibitors?
Uncoating is prevented by ion channel (M2) inhibitors; release of the virus from the cell membrane is inhibited by neuraminidase inhibitors
What is another name for Tamiflu? What kind of drug is it? What types of influenza can it treat?
Oseltamivir; neuraminidase inhibitor; type A and B
Are killed virus (inactivated), live virus (attenuated) or both types of vaccine used against influenza?
Both types are used
What is the formulation strategy for the influenza vaccine?
The most prevalent strain of H1N1 (type A), H3N2 (type A), and type B influenza are selected for the vaccine
What is the field of mycology about?
Fungi
What is the differentiation between yeasts and molds?
Yeasts are budding unicellular organisms that look sort of like bacteria, while molds have a long fluffy appearance and are multicellular
What does it mean for a fungus to be dimorphic?
It acts as a yeast in the body, but as a mold in the environment
What is a hypha?
A long branching structure of a fungus
Of the following, which are systemic dimorphic endemic fungi, and which are opportunistic?
– Histoplasma
– Candida
– Cryptococcus
– Blastomyces
– Aspergillus
– Histoplasma - systemic dimorphic endemic
– Candida - opportunistic
– Cryptococcus - opportunistic
– Blastomyces - systemic dimorphic endemic
– Aspergillus - opportunistic
Of the following, which are systemic dimorphic endemic fungi, and which are opportunistic?
– Coccidiodes
– Paracoccidioides
– Mucorales
– Penicillium
– Coccidiodes - systemic dimorphic endemic
– Paracoccidioides - systemic dimorphic endemic
– Mucorales - opportunistic
– Penicillium - systemic dimorphic endemic
Where do Trichophyton and Malassezia infect the body? What kind of organism are they?
Skin; they are superficial dermatophytic fungi
Are all fungi eukaryotic?
Yes
What is the analog of cholesterol used in the cell membrane of fungi?
Ergosterol
A 30 year old patient on total parental nutrition with this organism growing on culture of peripheral blood likely has …?
Candida albicans—recall that patients on total parenteral nutrition are at risk for bloodstream infections, and that C. albicans can grow in a hyphae form
Does Candida albicans grow on blood cultures?
Yes
What are pseudohyphae?
Chains of individual budding cells with constrictions seen in some fungi
What are these structures? What kind of organisms would form it?
Pseudohyphae; fungi like C. albicans
Can C. albicans grow as a unicellular yeast, pseudohyphae, or hyphae forms within the body (or some combination of them)? Can it form chlamydospores?
Yes to all forms; yes, it can form chlamydospores
What is this fungal infection?
Oral thrush or candidiasis
What is a pharmacological risk factor for vulvovaginal candidiasis in patients with normal immune systems?
Taking antibiotics, which eliminates the normal flora
What fungal infection can cause these skin manifestations?
C. albicans
What organism causes diaper rash?
C. albicans
Which Candida species is most significant in bloodstream infections?
C. albicans
If this infection on the liver is seen during surgery, with the following features seen in pathology, what is suspected?
Candida albicans
What are four risk factors for systemic candidiasis?
Neutropenia, catheters, parenteral nutrition, and broad-spectrum antibiotics
Can this infection be found in an immunocompetent host?
Yes, but it is much more common in AIDS patients (oral thrush)
How is a C. albicans infection treated?
Amphotericin, fluconazole, or echinocandins
