Micro FA Virology p162 - 178 Flashcards
What is recombination
Exchange of genes between 2 chromosomes by crossing over within regions of significant base sequence homology.
What quality of virus genomes has potential to cause antigenic shift?
Viruses with segmented genomes can go through reassortment to create new antigens.
Ex of segmented viruses
They include Bunyaviruses (3 segments), Orthomyxoviruses (influenza viruses) (8 segments), Arenaviruses (2 segments), and Reoviruses (10-12 segments).
Hepatitis D virus requires the presence of hepatitis B for what? What is that process called?
Hepatitis D virus requires the presence of replicating hepatitis B virus to supply HBsAg, the envelope protein for HDV. Called complementation
Define complementation
When 1 of 2 viruses that infect the cell has a mutation that results in a nonfunctional protein, the nonmutated virus “complements” the mutated one by making a functional protein that serves both viruses.
Which DNA virus has ssDNA?
Parvo
Which 3 DNA viruses have circular genomes?
Papilloma, Polyoma, Hepadna
Which RNA virus is double stranded?
Reo
⊕ stranded RNA viruses?
I went to a retro (retrovirus) toga (togavirus) party, where I drank flavored (flavivirus) Corona (coronavirus) and ate hippie (hepevirus) California (calicivirus) pickles (picornavirus).
Purified nucleic acids of most ____ viruses and _______ (≈ mRNA) viruses are infectious.
Which virus’ naked dsDNA are not infectious?
Purified nucleic acids of most dsDNA viruses (except poxviruses and HBV) and ⊕ strand ssRNA (≈ mRNA) viruses are infectious.
Naked nucleic acids of ⊝ strand ssRNA and dsRNA viruses are not infectious. why?
They require polymerases contained in the complete virion.
DNA viruses tend to have what shape? except?
icosahedral, except pox
Which DNA virus does not replicate in the nucleus
Pox - carries its own DNA-dep RNA polymerase
flesh colored papule with central umbilication - disease? virus?
Molluscum contagiousum - Pox virus
Which hepatitis virus has DNA?
HBV - Hepadna family
Adenovirus causes?
Febrile pharyngitis —sore throat
Acute hemorrhagic cystitis
Pneumonia
Conjunctivitis—“pink eye”
Gastroenteritis
Myocarditis
Which serotypes of HPV assoc with cervical cancer?
16,18 (31,35)
Pathomech of warts?
hyperkeratosis
Which viruses are DS and circular?
Papilloma & Polyoma (JC/BK)
What do JC/BK viruses cause?
JC virus—progressive multifocal leukoencephalopathy (PML) in HIV
BK virus—transplant patients, commonly targets kidney
JC: Junky Cerebrum; BK: Bad Kidney
what cell type does Parvovirus infect? consequences?
RBC precursors and endothelial cells; RBC destruction in fetus leads to hydrops fetalis and death, in adults leads to pure RBC aplasia and rheumatoid arthritis–like symptoms
Issue with parvovirus and sickle cell?
Aplastic crises
B19 causes what in children?
Fifth disease/erythema infectiosum - slapped cheek rash, lacy reticular rash on body
How does B19 infect RBC precursors?
by binding P antigen on RBCs
Properties of Herpes family of viruses
dsDNA, linear, enveloped
Encephalitis of HSV1 is localized to what area?
temporal lobe NOTE - Most common cause of sporadic encephalitis, can present as altered mental status, seizures, and/or aphasia.
HSV1 causes?
Gingivostomatitis, keratoconjunctivitis , herpes labialis , herpetic whitlow on finger, temporal lobe encephalitis, esophagitis, erythema multiforme.
Where does HSV1 & HSV2 lie latent?
HSV1 - trigeminal ganglia HSV2 - sacral ggl
T or F Viral meningitis more common with HSV1 vs HSV2
F - HSV2 is the more common viral meningitis
The Vaccine for papilloma virus contains which serotyes
capsid proteins from serotypes 6,11,16,18
How does papilloma virus –> cancer?
Viral oncoproteins E6 & E7 –> cell cycle dysregulation
E6 - binds to and promotes degradation of p53
E7 - binds and (-) p105Rb (retinoblastoma)
Virulence factors of Adenovirus (not in FA)
Penton fibers - a hemagglutinin, cytotoxic
E3 prot - (-) MHC1 expression
E1A prot - makes cells susceptible to TNF
Most common complication of shingles?
post-herpetic neuralgia
What does HHV3/VZV cause?
Varicella-zoster (chickenpox, shingles), encephalitis, pneumonia
For VZV, _____ branch involvement can cause herpes zoster _________.
CN V1 branch involvement can cause herpes zoster ophthalmicus.
Where does VZV lie latent?
dorsal root or trigeminal ggl
EBV/HHV4 is connected with which neoplasias?
Lymphoma (esp endemic Burkitt lymphoma) and nasopharyngeal carcinoma (Asians)
Nasopharyngeal CA - presents with nasal stuffiness and hearing loss bc blocks Eustachian tube. cytokeratin (+)
A pt diagnosed with EBV - the blood smear shows atypical lymphoctes - what type of cells are these?
Atypical lymphocytes on peripheral blood smear G—not infected B cells but reactive cytotoxic T cells. aka Downey cells
What cell does EBV infect? and how?
Infects B cells thru CD21 - “Must be 21 to drink Beer in a Barr.”
Sx of Mono
—fever, hepatosplenomegaly , pharyngitis, and lymphadenopathy
Which lymph nodes most commonly enlarged in Mono
posterior cervical nodes
A pos Dx for Mono involves a Monospot test - how does it work?
heterophile antibodies detected by agglutination of sheep or horse RBCs.
What drug, if used with Mono, leads to a maculopapular rash?
amoxicillin
EBV is assoc with what in AIDS pts?
hairy oral leukoplakia (hyperproliferation of oral epithelium)
1 in utero infection in US?
CMV
How does Congenital CMV/HHV5 present?
microcephaly,
sensorineural deafness
thrombocytic purpura (blueberry muffin baby - also in Rubella, but that’s not commonly seen in US unless unvaccinated)
periventricular brain calcification hepatosplenomegaly
How does CMV present in immunocompetent vs immunocompromised?
(-) Monospot Mono in immunocompetent
infection in immunocompromised -
Esp pneumonia in transplant pt
esophagitis
AIDS retinitis: hemorrhage, cotton wool exudates, vision loss
Where does CMV lie latent?
mononuclear cells
Major histo finding of CMV?
Owls eye inclusions in infected cells (SIGHT-omegalovirus - also good to remember AIDS retinitis)
What does HHV6 & 7 cause?
Roseola infantum (exanthem subitum): high fevers for several days that can cause seizures, followed by diffuse macular rash (starts on trunk then spreads to extremities ROSeoLA: fever first, ROSy (rash) LAter
Is HHV6 or 7 a more common cause of Roseola infantum?
HHV6
Dark/violaceous plaques or nodules representing vascular proliferations? What is it? virus and pt pop?
HHV8 - Kaposi sarcoma, a neoplasm of endothelial cells Seen in AIDS/transplant pt
HHV8 can also affect which other areas?
GI and Lungs
Tx of HHV8
IFN alpha
Lung sx caused by HHV8 (not in FA, Uworldq)
Primary effusion lymphoma - large malignant lymphocytes in pleura effusion, B cell markers
Another disease caused by HHV8?
Multicentric Castleman disease - lymphoproliferative disease
Dx of Herpes encephalitis?
CSF PCR for herpes encephalitis.
What is a Tzanck test?
—a smear of an opened skin vesicle to detect multinucleated giant cells commonly seen in HSV-1, HSV-2, and VZV infection.
Test of choice for herpetic skin lesions?
PCR
What histo characteristic is seen in HSV1,HSV2, and VZV?
Intranuclear eosinophilic Cowdry A inclusions
Receptor used by CMV?
Integrins - heparan sulfate
Receptor used by EBV?
CD21
Receptor used by HIV?
CD4, CXCR4, CCR5
Receptor used by Parvovirus B19?
P Ag on RBCs
Receptor used by Rabies virus?
Nicotinic AchR
Receptor used by Rhinovirus?
ICAM-1
Which RNA virus is double stranded?
Reo
Which RNA viruses are naked?
Picorna, Hepe, Calici, Reo (Picture a Hepe (happy) naked Calici in Reo)
T or F there are no naked helical RNA viruses
True! Helical viruses must be enveloped
Which RNA viruses are + sense?
Picorna
Hepe
Calici
Flavi
Corona
Retro
Toga
Picture a Positively Hepe Calici drinking a Flavorful Corona at a Retro Toga party!
Diseases caused by Reovirus?
COLTIvirus—COLorado TIck fever
Rotavirus—cause of fatal diarrhea in children
Picorna virus family causes?
Poliovirus—polio-Salk/Sabin vaccines—IPV/OPV Echovirus—aseptic meningitis
Rhinovirus—“common cold”
Coxsackievirus—aseptic meningitis; herpangina (mouth blisters, fever); hand, foot, and mouth disease; myocarditis; pericarditis
HAV—acute viral hepatitis
1 cause of aseptic meningitis and viral myocarditis?
Picorna - Echovirus/Coxsackie
1 viral cause of infection necessitating a heart transplant?
Coxsackie (myo/pericariditis)
1 cause of noninflammatory gastroenteritis in US? what family?
Norovirus (cruise ships); Calici
Viruses and diseases caused by flavi virus family?
HCV
Yellow fever
Dengue
St. Louis encephalitis
West Nile virus—meningoencephalitis, flaccid paralysis
Zika virus
Diseases caused by Toga virus family?
Toga CREW—Chikungunya virusa (co-infection with dengue virus can occur), Rubella, Eastern and Western equine encephalitis
What does the capsid look like for HIV virus?
complex and conical
Where do retroviruses replicate and how?
In the nucleus, w/ rev transcriptase
What neoplasia is assoc with retroviruses?
HTLV - T cell leukemia
What is caused by corono viruses?
“Common cold”, SARS, MERS
Difference between onset of common cold of Rhino v Corona viruses?
Rhino - summer/fall
Corona - winter/sprin
ss-linear helical 8 segmented RNA, w/ envelope - what family? major virus?
Orthomyxovirus; Influenza
Which RNA viruses are neg sense?
They include Arenaviruses, Bunyaviruses, Paramyxoviruses, Orthomyxoviruses, Filoviruses, and Rhabdoviruses.
Always Bring Polymerase Or Fail Replication.
Diseases caused by Paramyxo viruses?
PaRaMyxovirus:
Parainfluenza—croup
RSV—bronchiolitis in babies
Measles, Mumps
Diseases caused by ss- 3 segmented circular helical capsid virus family?
Bunya
California encephalitis
Sandfly/Rift Valley fevers
Crimean-Congo hemorrhagic fever
Hantavirus—hemorrhagic fever, pneumonia
Diseases caused by 2 segmented circular helical capsid RNA viruses? family?
Arena viridae
LCMV—lymphocytic choriomeningitis virus
Lassa fever encephalitis—spread by rodents
Filo virus - what diseases?
Ebola/Marburg hemorrhagic fever—often fatal.
Which RNA viruses are segmented?
All are RNA viruses. They include Bunyaviruses (3 segments), Orthomyxoviruses (influenza viruses) (8 segments), Arenaviruses (2 segments), and Reoviruses (10-12 segments).
ABOR - (2,3,8,10-12)
This Segment is A-BORing!!
How do Picorna viruses make viral proteins?
RNA is translated into 1 large polypeptide that is cleaved by virus-encoded proteases into functional viral proteins.
Which picorna viruses cause meningitis? Which are enteroviruses?
All are enteroviruses, that cause aseptic (viral) meningitis (except rhinovirus and HAV).
Why is Rhino virus not an enterovirus?
Acid labile—destroyed by stomach acid; therefore, does not infect the GI tract
Reservoir and vector of Yellow fever? what virus family?
A flavivirus transmitted by Aedes mosquitoes. Virus has a monkey or human reservoir
Sx of yellow fever?
high fever, black vomitus, and jaundice.
eosinophilic apoptotic globules seen on liver biopsy? - what are they? what disease
Councilman bodies
Seen in yellow fever, most famously. but also in other viral hemorrhagic fever/acute viral hepatitis
segmented dsRNA virus?
Reovirus
Major cause of acute diarrhea in children, esp in winter
Rota virus
The villous destruction and atrophy in GI by rota virus leads to?
dec absorption of Na+ and loss of K+
Virulence factors of influenza viruses? how do they work?
Contain hemagglutinin (binds sialic acid and promotes viral entry) and neuraminidase (promotes progeny virion release) antigens.
Patients with influenza are at risk for what infections
Patients at risk for fatal bacterial superinfection, most commonly S aureus, S pneumoniae, and H influenzae.
Explain genetic shift vs drift
Genetic shift
Causes pandemics. Reassortment of viral genome segments, such as when segments of human flu A virus reassort with swine flu A virus.
Genetic/antigenic drift
Causes epidemics. Minor (antigenic drift) changes based on random mutation in hemagglutinin or neuraminidase genes.
Explain two types of influenza vaccine
Killed viral vaccine is most frequently used.
Live attenuated vaccine contains temperaturesensitive mutant that replicates in the nose but not in the lung; administered intranasally.
Sx of Rubella - what virus family?
Toga;
Fever, postauricular and other lymphadenopathy, arthralgias, and fine, maculopapular rash that starts on face and spreads centrifugally to involve trunk and extremities
Congenital Rubella looks like what?
Congenital rubella findings include “blueberry muffin” appearance due to dermal extramedullary hematopoiesis.
parainfluenza (croup), mumps, measles, RSV are all from what family? what do they all cause?
Paramyxoviridae;
all cause resp tract infections (bronchiolitis, pneumonia) in children/infants
Virulence factor of Paramyxovirus - what does it cause? Name a drug that targets it?
All contain surface F (fusion) protein, which causes respiratory epithelial cells to fuse and form multinucleated cells.
Palivizumab (monoclonal antibody against F protein) prevents pneumonia caused by RSV infection in premature infants. Palivizumab for Paramyxovirus (RSV) Prophylaxis in Preemies.
Acute laryngotracheobronchitis is caused by what virus?
parainfluenza virus - croup
Virulence factors of Parainfluenza virus and fxn?
Virus membrane contains hemagglutinin (binds sialic acid and promotes viral entry) and neuraminidase (promotes progeny virion release) antigens
Severe croup can lead to what circulatory issue? why?
Severe croup can result in pulsus paradoxus 2° to upper airway obstruction.
Xray finding of croup?
Narrowing of upper trachea and subglottis leads to characteristic steeple sign on x-ray
Sx of parainfluenza?
“seal-like” barking cough and inspiratory stridor.
4 Cs of Measles?
4 C’s of measles: Cough Coryza Conjunctivitis “C”oplik spots
Administration of this vitamin can help reduce mortality from measles
Vitamin A; esp in malnourished children
Sx of measles
Usual presentation involves prodromal fever with cough, coryza, and conjunctivitis, then eventually Koplik spots followed 1–2 days later by a maculopapular rash that starts at the head/neck and spreads downward.
Diff in rash in Measles vs Rubella
Measles - maculopapular rash B that starts at the head/neck and spreads downwards
Rubella - maculopapular rash that starts on face (day 1) and spreads centrifugally to involve trunk and extremities (day 3)
Describe a Koplik spot
bright red spots with blue-white center on buccal mucosa
Patho signs of Measles
Lymphadenitis with Warthin-Finkeldey giant cells (fused lymphocytes) in a background of paracortical hyperplasia.
Sequelae of Measles
SSPE (subacute sclerosing panencephalitis, occurring years later)
Encephalitis (1:2000)
Giant cell pneumonia (rare except in immunosuppressed)
Patho signs of Measles
Lymphadenitis with Warthin-Finkeldey giant cells (fused lymphocytes) in a background of paracortical hyperplasia
Most common cause of death in childhood measles?
Pneumonia
Sx of Mumps
Parotitis A, Orchitis (inflammation of testes), aseptic Meningitis, and Pancreatitis
Can cause sterility (especially after puberty)
What are the cytoplasmic inclusions in Rabies virus called, and what cells do they infect?
Negri bodies commonly found in Purkinje cells of cerebellum and in hippocampal neurons.
Postexposure prophylaxis of Rabies? What type of immunity is this?
Postexposure prophylaxis is wound cleaning plus immunization with killed vaccine and rabies immunoglobulin.
passive-active immunity.
How does the rabies virus infect the CNS?
Travels to the CNS by migrating in a retrograde fashion (via dynein motors) up nerve axons after binding to ACh receptors.
Progression of Rabies disease?
Progression of disease: fever, malaise –> agitation, photophobia, hydrophobia, hypersalivation –> paralysis, coma –> death.
Common transmission of rabies in US?
Infection more commonly from bat, raccoon, and skunk bites than from dog bites in the United States;
Raccoon - Eastern US; Skunk - Western US
aerosol transmission (eg, bat caves) also possible.
Ebola virus - what virus family? what cell types does it infect?
A filovirus that targets endothelial cells, phagocytes, hepatocytes.
Sx of Ebola virus
Following an incubation period of up to 21 days, presents with abrupt onset of flu-like symptoms, diarrhea/vomiting, high fever, myalgia. Can progress to DIC, diffuse hemorrhage, shock.
Transmission of Rabies
Transmission requires direct contact with bodily fluids, fomites (including dead bodies), infected bats or primates (apes/monkeys);
Zika virus - what virus family? transmitted by?
A flavivirus most commonly transmitted by Aedes mosquito bites
If transmitted in utero - consequences of Zika?
Can lead to congenital microcephaly or miscarriage if transmitted in utero.
Sx of Zika virus?
conjunctivitis, low-grade pyrexia, and itchy rash in 20% of cases.
Sx same for all hepatitis viruses?
episodes of fever, jaundice, Inc ALT and AST.
Which hepatitis viruses are naked ?
HAV, HEV
Naked viruses are usually stronger, and can last through gastric acid
Which Hepatitis virus has DNA ?
HBV
How does HBV reproduce?
HBV DNA polymerase has DNA- and RNA-dependent activities. Upon entry into nucleus, the polymerase completes the partial dsDNA. Host RNA polymerase transcribes mRNA from viral DNA to make viral proteins. The DNA polymerase then reverse transcribes viral RNA to DNA, which is the genome of the progeny virus.
What leads to the antigenic variation of HCV?
HCV lacks 3′-5′ exonuclease activity –> no proofreading ability –> antigenic variation of HCV envelope proteins
Which Hepatitis viruses are ss+ linear RNA with an icosahedral capsid? Which one is not naked?
HAV, HEV, HCV - HCV has an envelope
Which Hepatitis virus is ss- circular?
HDV
Which two hepatitis viruses can lead to carcinoma?
HBV HCV
Liver biopsy in HAV shows?
Hepatocyte swelling, monocyte infiltration, Councilman bodies
Liver biopsy in HBV shows?
Granular eosinophilic “ground glass” appearance; cytotoxic T cells mediate damage
Liver biopsy in HCV shows?
Lymphoid aggregates with focal areas of macrovesicular steatosis
Which two hepatitis viruses can result in a carrier state?
HBV, HCV
Hematological/Vascular issues assoc of HBV vs HVC
HBV - assoc w/ PAN
HCV - Essential mixed cryoglobulinemia, Inc risk B-cell NHL, ITP, autoimmune hemolytic anemia
Which types of glomerulonephritis are common with HBV vs HCV?
Membranous > membranoprolif with HBV
Membranoproliferative >membranous with HCV
Which Hepatitis induced GN is seen with subepithelial deposits and which with subendothelial deposits? Which has GBM thickening vs GBM splitting?
Membranous nephropathy (HBV>HCV) – spike and dome subepithelial deposits, GBM thick
Membranoproliferative (HCV>HBV) – subendothelial deposits with granular IF, GBM split
Vascular manifestations of HBV vs HCV?
HBV - PAN
HCV - Leukocytoclastic vasculitis
Which Hepatitis virus has derm manifestations?
HCV - porphyria cutanea tarda, lichen planus
HBV - serum sickness like rash
Endocrine risks with HCV
Inc risk of DB, Autoimmune hypothyroidism
Is HIV diploid or haploid? RNA or DNA?
a diploid RNA virus
Best test to detect acute Hep A infection
IgM vs Hep A
What protects against HAV reinfection?
IgG vs HAV
List the 3 Ag of HBV and what they indicate
HBsAg - surface Ag, indicates active infection
HBcAg - core HBV Ag
HBeAg - secreted by infected hepatocyte into circulation. indicates active viral replication, high tramissibility
Sign of actue/recent HBV infection
Igm vs HBcAg
What is the only marker of HBV infection in the window period?
IgM vs HBcAg
What does Anti-HBe indicate?
low transmissibility
What, on its own, indicates vaccination of HBV
Anti-HBs with no other markers
A pt who has recovered from HBV has what markers?
Anti-HBs IgG and Anti-HBe IgG
Which HBV Antibody rises first?
Anti-HBc
What does the HBV window mean?
The time between the dec in HBsAg and the appearence of Anti-HBs
Where are HIV envelope proteins acquired from?
from budding off host cell plasma membrane
Where are gp120 and gp41 of HIV derived from?
Formed from cleavage of gp160 to form envelope glycoproteins
Which HIV protein mediates attachment to host CD4 T cell?
gp120
Which HIV protein enables viral fusion and entry?
gp41
What gene codes for HIV capsid and matrix proteins? what are those proteins
gag gene; capsid prot = p24
matrix prot = p17
What does HIV pol gene code for?
pol—Reverse transcriptase, Integrase, Protease; RIP “Pol” (Paul)
How does HIV integrate its genes into the host genome?
Reverse transcriptase synthesizes dsDNA from genomic RNA; dsDNA integrates into host genome.
What does HIV bind to on T cells? What’s the co-receptor?
CD4 and CXCR4 on T cells
Where/When does HIV bind to CCR5?
It binds to CCR5 on macrophages in early infection
What could lead to HIV immunity or slower course of infection?
Homozygous CCR5 mutation = immunity. Heterozygous CCR5 mutation = slower course.
What do we use to detect HIV in babies?
HIV-1/2 Ag/Ab testing is not recommended in babies with suspected HIV due to maternally transferred antibody. Use HIV viral load instead.
What test do we use Dx HIV and what are we testing for?
Presumptive diagnosis made with HIV-1/2 Ag/ Ab immunoassays. These immunoassays detect viral p24 Ag capsid protein and IgG Abs to HIV-1/2.
What do we use to monitor effect of drug therapy in HIV? what does it test for?
Viral load; Viral load tests determine the amount of viral RNA in the plasma.
What determines someone has AIDS?
AIDS diagnosis ≤ 200 CD4+ cells/mm3 (normal: 500–1500 cells/mm3).
HIV ⊕ with AIDS-defining condition (eg, Pneumocystis pneumonia) or CD4+ percentage < 14%.
What is HIV virus doing during latency period
replicating in lymph nodes
What infections do we watch out for when CD4 count drops below <500? How do they present?
AIDS diseases w/ CD <200
AIDS disease assoc w/ CD# <100 - fungi/parasites. How does it present?
AIDS diseases CD# < 100 - bact/viruses; Presentation
Prion diseases caused by?
Prion diseases are caused by the conversion of a normal (predominantly α-helical) protein termed prion protein (PrPc) to a β-pleated form (PrPsc), which is transmissible via CNS-related tissue (iatrogenic CJD) or food contaminated by BSE-infected animal products (variant CJD)
Accumulation of PrPsc results in ?
Accumulation of PrPsc results in spongiform encephalopathy and dementia, ataxia, and death.
PrPsc resists ______ ________ and facilitates the conversion of still more PrPc to PrPsc. Resistant to standard sterilizing procedures, including standard ___________.
PrPsc resists protease degradation and facilitates the conversion of still more PrPc to PrPsc. Resistant to standard sterilizing procedures, including standard autoclaving.
