Virology Flashcards
Name 3 Enteroviruses
- Coxsakie A and B
- Echoviruses
- Polioviruses
What as the sensivitiy of CSF culture for enteroviral meningitis?
50-70%
Due to low titres of virus in the CSF and coxsackie A virus may not grow in culture
How long does it take for CSF culture for enterovirus to become positive?
3-4 days, can take up to 7-10 days
What is enterovirus season?
Summer/Fall
Why is serology not useful for enterovirus diagnosis? (3 reasons)
- Antigenic diversity of the enteroviruses
- A rise in Ab titers may take several weeks before convalescent serum is available
- IgM Ab assays are not widely available
What is the target for enterovirus PCR?
5’ noncoding region, conserved among most serotypes
What % of viral meningitis is caused by HSV?
1-5%
List 3 differences between HSV meningitis and HSV encephalitis
- HSV meningitis is usually HSV-2, encephalitis is usually HSV-1
- Meningitis is self limited, encephalitis is necrotizing
- HSV can sometimes be cultured from CSF in meningitis, but rarely in encephalitis
True or False: VZV meningitis can occur as a complication of varicella or zoster?
True
Name 2 viruses in the Arenaviridae family.
- Lassa fever virus
2. Lymphocytic choriomeningitis virus (LCM)
How are humans infected with Lymphocytic choriomeningitis virus?
Contact with mice or hamsters
4 viruses associated with acute transverse myelitis.
- CMV
- EBV
- VZV
- Enteroviruses
4 viruses associated with Guillain-Barre syndrome.
- CMV
- EBV
- VZV
- HIV
What is the triad of ‘spongiform change’ on brain tissue when diagnosing CJD prion disease?
- Neuronal loss
- Reactive gliosis
- Neuronal vaculation
What protein is detected in the diagnosis of CJD?
14-3-3
What is SSPE?
Subacute sclerosing panecephalitis, caused by measles virus but presents years after infection. Caused by defective measle virus in the brain leading to production of nucleocapsid.
2 most common clinical syndromes caused by adenovirus
- Respiratory illness
- Childhood diarrhea
(Don’t forget pharyngoconjunctival fever and keratoconjunctivitis too)
Adenovirus:
RNA or DNA?
Envelope?
Morphology?
dsDNA
Nonenveloped
Icosahedral
What receptor does Adenovirus use to gain entry into cells and what other virus uses the same receptor?
CAR receptor (Coxsackie Adenovirus Receptor)
Also used by Coxsackie B virus
Infects corneal epithelium, upper and lower respiratory epithelium, urinary tract epithelium.
Can persist chronically in lymphocytes. Can find in many tissues and blood during disseminated disease.
What are the 2 most common serotypes of Adenovirus that cause gastroenteritis?
40 and 41
These infections can be asymptomatic
What age are Adenovirus infections most common?
6 months - 5 years
Many kids have seen 3 or 4 different Adeno infectious in this time
Who is at increased risk for severe Adenovirus infections?
Impaired cell-mediated immunity
Neonates, congenital immunodeficiencies, HSCT, HIV
How is adenovirus transmitted?
Direct contact, small droplet aerosols, fecal-oral, water
How long is adenovirus excreted after initial infection?
5-10 days in nasopharyngeal secretions
Weeks - months in stool
1-14 days with gastroenteritis from 40 or 41
What is the incubation period of adenovirus?
2-21 days (average 7-13 days)
How do laboratory values differ for Adenovirus compared to Flu and RSV?
In Adenovirus there is high WBC, ESR, and CRP.
Also they have high and persistent fever
What the most common cause of acute febrile tonsillitis?
Adenovirus
Which viral infection predisposes children to more severe adenovirus disease?
Measles, due to temporary suppression of cell mediated immunity during measles
Clinical symptoms of adenovirus gastroenteritis
Watery, nonbloody diarrhea lasting 3-11 days (longer than rota)
Fever and vomiting are common
Type 41 diarrhea lasts longer than type 40
What adenovirus serotype casues hemorrhagic cystitis?
11
Hematuria can last from 2 days to 2 weeks
How long after transplantation do adenoviral infections tend to occur
Peds - 30 days
Adults - 90 days
Thought to be due to latent virus
What cell lines can adenovirus be cultured from?
A549, HeLa, HEp-2, KP, MRC5
Serotypes 40 and 41 do not grow well in most cell lines
Can use shell vials
At CHEO they will grow it in HFL, RMK, MRC5
Is there a vaccine for Adenovirus?
Yes, it is approved for military recruits aged 17-50.
A tablet form, live oral vaccine for types 4 and 7. However now seeing more type 14
What is the treatment of Adenovirus?
There is not good treatment.
Ribavirin, ganciclovir, and cidofovir have variable activity
What parvoviruses cause infections in humans?
- Parvovirus B19 (genus Erythrovirus)
- Human bocavirus (genus Bocavirus)
- Adeno Associated Viruses (genus Dependovirus)
- PARV4 and PARV5 (no genus)
Parvovirus:
RNA or DNA?
Envelope?
Morphology?
ssDNA
Nonenveloped
Icosahedral
What is the receptor for parvovirus B19?
Globoside or P antigen
What tissues does parvovirus B19 infect?
Bone marrow, erythroid precursor cells
Also fetal liver in utero
In what cell lines can Parvoviruses grow?
B19 - Human leukemic cell lines as it needs erythropoietin
Bocavirus - no cell lines
AAV - many lines as long as it has the appropriate helper virus
What is the rash associated with parvovirus B19 called?
Erythema infectiosum (fifths disease)
Asymptomatic infections are common
The rash comes at the end of the illness
What season are parvovirus infections most common?
Late winter and spring
What is the frequency of vertical transmission when a mother is infected during pregnancy?
25-50%
2-10% lead to fetal death
If the fetus survives there is no increased risk for birth defects
How is parvovirus B19 infection acquired?
Respiratory, close contacts, droplets, fomites
What is the incubation period of parvovirus B19?
1-2 weeks
Signs and symptoms of parvovirus B19 infection?
Fever, malaise, rash, arthritis
Decreased Hb, WBC, Platlets and neutrophils
When do IgM and IgG appear for parvovirus B19?
IgM - 10-14 days after innoculation
IgG - 14 days after innoculation
What illness does human bocavirus cause?
Respiratory illness
How is parvovirus B19 diagnosed?
Virus isolation is not efficient Antigen detection - Immunohistochemistry PCR Antibody Assays - IgM and IgG IgM usually positive by the time of the rash
What is the treatment of parvovirus B19?
Transient aplastic crisis - requires transfusions
IVIG
How many serological groups of Rotavirus have been identified and which cause human infection?
6 (A-F)
A, B, C cause human infection
Group A is the most common
What is the season for rotavirus?
Winter
How is rotavirus diganosed the laboratory?
- Antigen detection (EIA or latex agglutination). All assays detect the group antigens
- EM
- Electropherotyping - looks at the migration pattern of the 11 genome segments in a gel
Cell culture is difficult
What family of viruses does Ebola belong to?
Filoviridae
What 4 tests for Ebola virus are offered in Canada, and on what specimens?
At the NML Speicla Pathogens Level 4 lab:
- IgG and IgM serology
- Viral antigen ELISA on serum
- PCR on whole blood
- Virus isolation from whole blood (Electron Microscopy and culture in Vero cells or mouse innoculatoin)
How are people exposed to Hantavirus?
Urine, saliva, or droppings from infected rodents.
Has been identified in Deer Mice in Canada
How are people exposed to Hantavirus?
Urine, saliva, or droppings from infected rodents.
Has been identified in Deer Mice in Canada
How long after exposure do the symptoms of Hantavirus develop?
1-6 weeks
Patients develop a pulmonary syndrome (HPS)
How long after exposure do the symptoms of Hantavirus develop?
1-6 weeks
Patients develop a pulmonary syndrome (HPS)
Lassa Fever Virus:
- RNA or DNA?
- Envelope?
- Family?
- Single strand RNA virus in 2 segments
- Enveloped
- Arenaviridae
What are 4 target cells for Lassa Virus?
Endothelial cells
Monocytes
Dendritic Cells
Macrophages
Name 5 viral hemorrhagic fevers.
- Ebola Virus Disease
- Lassa
- Crimean-Congo
- Marburg Bolivian (Machupo)
- Venezuelan
How many days after exposure do symptoms of Ebola virus develop?
2-21 days
How is Ebola virus transmitted?
Contact and Droplet, both directly and indirectly.’
Possible aerosols with prominent cough, vomit, diarrhea or hemorrhage - that’s why an N95 mask is suggested (contact, droplet, and airborne isolation.
Family and Genus of Crimean-Congo Hemorrhagic fever?
Family Bunyaviridae, Genus Nairovirus
Most common way the Crimean-Congo Hemorrhagic fever is transmitted?
Tick bites.
Also from contact with viremic blood from infected humans or animals
What is the incubation period for Norovirus?
10-51 hours
Causes 58% of food borne infections
How long after infections do people shed Norovirus in the stool for?
20-40 days
Longer in immunocompromised
Which Norovirus Genogroups cause disease in humans?
Which is the most common?
GI, GII, GIV
GII.4 (genotype 4)
What is the receptor for human norovirus and what cells is it on?
Histoblood group antigens (HBGA)
Found on erythrocytes, epithelial cells and in saliva and breastmilk. Secreters of HBGA are more susceptible to Norovirus than are non secretors
Norovirus:
RNA or DNA?
Envelope?
Morphology?
ss(+)RNA
Nonenveloped
Protein capsid outer shell has 32 cup like indents and icosohedral symmetry
What is the infectious dose for Norovirus?
<10 viral particles, low!
Norovirus testing limitations for:
a) culture
b) EM
c) Antigen detection
d) PCR
a) Does not grow in culture
b) Small number of viral particles
c) Large antigenic variety, no cross reacting antibodies to detect all strains
d) Many different strains with low sequence homology
What vaccines are in the works for Norovirus?
Protein based subunit VLP vaccine - uses the VP1 capsid protein
Live vector vaccine
What 4 steps in the viral life cycle do antiretrovirals work for HIV?
- Entry
- Reverse Transcription
- Integratoin
- Proteolytic Processing
List 7 NRTIs
- Zidovudine (AZT)
- Stavudine (d4T)
- Didanosine (ddI)
- Lamivudine (3TC)
- Emtricitabine
- Abacavir (ABC)
- Tenofovir
List 5 NNRTIs
- Neverapine
- Efavirenz
- Delavirdine
- Etravirine
- Rilpivirine
What is the most frequent non-cutaneous site of varicella zoster infection involvement?
CNS - Cerebellar ataxia
7-21 days post. With vomiting, altered speech, fever, vertigo and tremor
Also encephalitis, transverse myelitis, meningitis, Reyes
Aside from CNS complications, what are 5 other complications of VZV infection?
Pneumonitis Myocarditis Hepatitis Nephritis DIC
Time frame of Mom’s infection which has the highest rate of infant mortality?
5 days prior to delivery and 48 hours post delivery
4 findings in congenital VZV infection?
- Hypoplastic extremities
- Skin scarring
- Eye abnormalities
- CNS impairments
3 findings in Ramsay Hunt Syndrome?
- Ipsilateral facial palsy
- External auditory meatus vesicles
- Lack of taste on anterior 2/3 of the tongue
3 indications for VZIG?
Exposure >1 hr of contact with a VZV infected person for:
- Pregnant woman who are seronegative or no previous history of VZ
- Immunocompromised children <15 with no prior exposure
- Baby of a mother who developed VZ 5 days prior or 48 hours after delivery
Definition for Chronic Hepatitis B
Hepatitis B surface antigen (HbsAg) positive for >6 months
Percentage of hepatitis B carriers that will develop serious sequelae during their lifetime?
15-40%
Liver cirrhosis, decompensation or hepatocellular carcinoma
Definition of High, Intermediate, and Low prevalence of Hepatitis B Virus for countries?
Based on the prevalence of surface antigen:
Low =8%
What is the risk for developing chronic Hep B after acute exposure for:
a) Neonates with HbeAg + mother
b) Infants and children <5 years old
c) Adults?
a) Neonates HBeAg + mom = 90%
b) Infants and children = 25-30%
c) Adults = <5%
4 reasons for isolated Hepatitis B core antibody (Anti-HBc) positive?
1) Chronic Hep B infection where the sAg has fallen below the level of detection (can probably still detect HBV DNA, mores in the liver). Not uncommon in those from high prevalence areas, HIV or Hep C co-inifected.
2) Immunity from prior infection, but sAb has fallen below the level of detection. With a dose of Hep B vaccine sAb may become positive again.
3) False positive Anti-HBc
4) Window period during acute hepatitis B (between surface Ag negative and sAb positive). Should be AntiHBc-IgM positive.
Recommendations for newborns of HBsAg positive mothers discovered in pregnancy?
Hep B vaccine at birth
HBIG at birth
95% efficacy if HBV DNA of mother is <10^8
Why is plasma used for CMV PCR instead of whole blood?
Latent CMV virus can be detected in whole blood as it can reside latent in PMNs and monocytes.
What family and genus does the orf virus belong to?
Family = Poxviridae Genus = Parapoxvirus
2 clinical syndromes that have been associated with parapoxvirus infections?
1) Erythema multiform
2) Stevens-Johnson syndrome
Famiy of molluscum contagiousum?
Poxviridae
What are the 3 main genes in HIV-1 and what do they code for?
1) Core (gag) = structural proteins (p17, p24, p7, p9)
2) Polymerase (pol) = protease, reverse transcriptase, RNAase, integrase
3) Envelop (env) = envelope glycoproteins (gp160=gp120/41)
What are the major gene product difference between HIV1 and HIV2?
env = envelope glycoproteins HIV 1 = gp160 = gp120/41 HIV 2 = gp125 = gp105/36 pol = HIV 1 Reverse Transcriptase = p66, p51 HIV 2 Reverse Transcriptase = p68 HIV 1 Endonuclease = p32 HIV 2 Endonuclease = p33 gag = HIV 1 Capsid = p24, HIV2 = p26 HIV 1 Matrix = p17, HIV2 = p16
3 functions of HIV Reverse Transcriptase
1) RNA dependant DNA Polymerase (makes cDNA)
2) RNase H (the chew up the RNA strand)
3) DNA dependant DNA Polymerase (duplicated cDNA)
What is a provirus?
Virus genome that is integrated into the hosts DNA
Geographic distribution of HIV2 infection?
West African
European immigrants from West Africa
Mozambique
Angola
What is the risk of HIV1 infection following occupational percutaneous exposure to infected blood?
0.3%
Following HIV1 infection what specific markers appear in the blood? List in chronological order.
1) HIV1 RNA (1 week after infection)
2) p24 Antigen (1-4 weeks)
3) HIV1 Antibody (1-2 months, but up to 6 months)
How long after infection with HIV1 virus before symptoms develop? (Incubation period)
3-6 weeks
Symptoms last 7-14 days
What are the 6 classes of HIV Antiretroviral drugs?
1) Nucleoside Reverse Transcriptase Inhibitors (NRTI)
2) NonNRTIs
3) Protease Inhibitors
4) Fusion Inhibitors
5) Integrase Inhibitors
6) CCR5 Inhibitors
What is unique about a 4th generation HIV test?
Detects IgG, IgM AND p24 antigen
The 3rd generation does not detect the p24 antigen
2nd generations do not detect IgM
Great picture of the different tests in CLSI M53
What test must be done before treating an HIV positive patient with Maraviroc?
CCR5 tropism assay. Maraviroc only works on isolates that are soley CCR5 tropic
What are the 3 groups of HIV1 infection? What is the most common?
Major (M) = A, B, C, D, F, G, H, J, K
Outlier (O)
Non M, Non-O (N)
M group, subtype B is the most common
HIV2 has 2 groups, A and B
What is a recombinant HIV virus that has been transmitted to 3 or more persons called?
Circulating Recombinant Form (CRF)
3 stages of HIV infection?
1) Acute Infection
2) Latent Phase
3) AIDS (CD4 <200, OI)
1 way to increase the sensitivity of p24 antigen assays?
Heat or acid to break up the antigen/antibody complexes
5 causes of brain lesions in AIDS patient?
1) Toxoplasma encephalitis
2) Primary CNS Lymphoma
3) Progressive multifocal leukoencephalopathy
4) HIV encephalopathy
5) CMV encephalitis
What is the incubation period for measles virus?
8-12 days
When are patients with measles virus contagious?
4 days before rash appearance to 4 days after rash appearance
Isolation requirements for measles?
Airborne until 4 days after rash onset
Or duration of illness if immunocompromised
Family and Genus for Measles virus?
Family = Paramyxoviridae Genus = Morbillivirus
When do IgG and IgM appear in measles infection?
3-7 days after the rash
Treatment for measles?
No antiviral treatment Vitamin A for once daily x 2 days: 200,000 IU for 12 months of age and older 100,000 IU for 6-12 months 50,000 IU for <6 months
Can give measles vaccine within 72 hours of exposure or IVIG within 6 days of exposure
3 clinical manifestations of HHV6 in an adult bone marrow transplant recipient?
1) Meningoencephalitis
2) Febrile illness
3) Pneumonitis
What animal was involved with the transmission of SARS?
Palm civet
Raccoon dog
4 most common comorbidities in patients with MERS CoV?
1) CKD
2) DM
3) Heart Disease
4) Immunocompromised
What is the receptor for MERS CoV in bronchiolar tissue?
DPP4 (CD26)