CMV, EBV, KSHV Flashcards
CMV, EBV, and human herpesvirus-8 or KSHV all fall into what category?
Human herpesviruses
What is the general structure of a herpesvirus?
Icosahedral capsid surrounded by a lipid envelope that contains about a dozen virus-encoded glycoproteins
What’s the genome of a herpesvirus like?
Large, linear, double stranded DNA (150-250 kbp)
Herpesvirus genomes are replicated in the (cytoplasm/nucleus).
Nucleus
Herpes viruses produce _________ in which the primary infection is often asymptomatic. But _________ can occur especially in immune-compromised hosts.
Self-limiting infections; life-threatening infections or cancers
What type of replication do herpesviruses undergo?
Lytic
Following virus attachment, penetration occurs by _________.
Virus glycoprotein-mediated fusion of envelope and plasma membrane
Herpesvirus penetration occurs by a (pH dependent/pH independent) event.
pH independent event
What happens after the released nucleocapsid gets in the cell?
- Migrates to nuclear envelope via microtubules
- Uncoats
- DNA enters the nucleus
- Virion components shut off host macromolecular synthesis
What are the parts of the cascade regulation of viral genes?
- Immediate early (IE) gene expression
- Early gene expression
- Late gene expression
- Virus assembly
- Virus particle release
What are immediate early genes?
Virus-specific transcription factors that use host RNA pol II and stimulate transcription at virus early promotors
What are early genes?
Genes that encode many nonstructural proteins and enzymes and use viral DNA pol and thymidine kinase
What are late genes?
Genes that encode structural proteins and are dependent on IE TFs plus genome replication for expression.
Viral glycoproteins can be transported to the infected cell surface where they cause _______.
Syncytia formation
Where in the cell does virus assembly occur?
In the nucleus where nucleocapsids bud first into the perinuclear space
T or F: All herpesviruses undergo latency.
T: entire genomes are maintained extrachromosomally in the host indefinitely, but no viruses are produced
What are the three stages of latency?
- Establishment
- Maintenance
- Reactivation
When does reactivation generally occur?
When there’s a lapse in immunity
Reactivation results in ______ and ______.
Production of virus particles and recurrent infection
T or F: Anyone infected with a herpesvirus is in the club fo life.
True dat (risk of recurrent infections or other sequelae)
What is acyclovir?
An antiviral prodrug that prevents chain elongation from continuing on an actively replicating virus
What are the alphaherpesvirinae (3)?
- HSV-1
- HSV-2
- VZV
The alphaherpesvirinae are (neurotropic/lymphotropic) for latency and have (aggressive/insidious) growth.
Neurotropic, aggressive
The betaherpesvirinae are (neurotropic/lymphotropic) for latency and have (aggressive/insidious) growth.
Lymphotropic, insidious
What are the betaherpesvirinae? (3)
- CMV
- HHV-6
- HHV-7
What are the gammaherpesvirinae? (2)
- EBV
2. HHV-8
The gammaherpesvirinae are (neurotropic/lymphotropic) for latency and have (aggressive/insidious) growth.
Lymphotropic, insidious
T or F: CMV is highly contagious.
F
CMV is more prevalent in (lower/higher) socioeconomic classes.
Lower (80% of adults in lower class, 50% of adults in higher class)
What are the general steps of the lytic cycle? (6)
- Virus attachment
- Penetration
- Uncoating
- Programmed expression of viral genes
- Assembly
- Release
Where is CMV found?
Saliva, urine, breastmilk, semen, cervical secretions, blood
Who’s the most at risk for CMV?
Neonates, day care workers, pregnant workers, immunocompromised patients, gay men
Neonatal CMV infections can result in ________.
Retardation and deafness
CMV infection occurs through _________.
Direct contact with secretions (not by aerosol)
Where is primary CMV replication taking place? Secondary?
Primary in epithelial cells followed by spread to lymphoid tissue
What do CMV-infected cells look like?
Large, puffed up
T or F: Most CMV infections in neonates and adults are asymptomatic.
T
Most _________ get CMV infection with pnemonitis.
Organ transplant patients. Don’t forget this!
AIDS patients are prone to CMV _____, _____, and ______.
Retinitis, colitis, pneumonitis
How can you diagnose CMV?
ELISA, PCR, Shell vial assay (indirect immunofluorescent used to detect an immediate early protein after 24 hours of cell culture infection)
What can you use to limit complications of CMV in transplant patients?
CMV Ig and ganciclovir
What is ganciclovir?
Guanosine analog that requires phosphorylation by viral kinase for activity
-Triphosphate form inhibitys CMV polymerase
What is the downside of the triphosphate form of ganciclovir?
It is more toxic to the host than acyclovir
Side effects of ganciclovir
Neutropenia and GI bleeding
_______ are approved for CMV retinitis treatment in AIDS patients.
Gancyclovir, Cidofovir, Foscarnet
What is foscarnet?
A pyrophosphate analog that inhibits DNA polymerase but doesn’t require phosphorylation for activity
What is cidofovir?
A competitive inhibitor of CMV DNA pol that does not require viral kinase action for activity (like ganciclovir does)
Who typically gets EBV infection at an early age?
People in a low socioeconomic setting
EBV can lead to what common disease?
Infectious mononucleosis
_____% of the adult population contains Ab to EBV.
95%
EBV can cause ________ in immunocompromised hosts.
Oral hairy leukoplakia (productive infection of tongue epithelial cells)
____________ from EBV is seen in some transplant patients.
Posttransplant lymphoproliferative disease (PTLD)
Which cancers is EBV associated with?
Burkitt’s lymphoma and nasopharyngeal carcinoma
How does EBV spread from person to person?
Through saliva by kissing <3
What is EBV’s incubation period?
4-7 weeks
Initial replication of EBV occurs in _______, then spreads to _______.
Initial replication in oropharyngeal epithelium –> lymphocytes –> liver and spleen
Where does EBV remain latent?
Throat epithelium and B cells
T or F: Oral shedding of EBV occurs for many months.
F: occurs for many weeks
T or F: Most EBV infections are asymptomatic.
T
What are the symptoms of infectious mononucleosis?
Sore throat, fever, malaise, lymphadenopathy
How can you diagnose EBV?
Symptoms and presence of at least 50% atypical large lymphocytes with lobulated nuclei
What is EBNA and what does it indicate?
An EBV antigenic marker
- EBNA 1 maintains genome replication in dividing B cells
- Conversion to anti-EBNA IgG indicates resolution of primary infection
Where will you find VCA?
It’s a viral capsid antigen on EBV
Anti-VCA IgM indicates _______.
Primary infection
Anti-VCA IgG without ________ indicates primary infection.
anti-EBNA
Anti-VCA IgGa with anti-EBNA indicates ______.
Past infection
Where will you detect EA (early antigen)?
In cells that do not produce virus
What does the monospot test look at?
Heterophile antibodies that agglutinate sheep RBCs (distinguishes EBV mono from CMV mono)
How do you treat oral leukoplakia?
Acyclovir
How do you treat PTLD?
Stop immunosuppression and monitor for rejection
What is PTLD?
Uncontrolled proliferation of B cells due to their transformation of EBV and no CTLs to control them
Where is Burkitt’s lymphoma endemic?
Central Africa and New Guinea
What three factors is Burkitt’s lymphoma associated with?
- Early EBV infection –> latency
- C-MYC activation
- Malaria
T or F: Association of nasopharyngeal carcinoma with EBV is worldwide.
T
Where does nasopharyngeal carcinoma have the highest frequency and what’s a possible reason for this?
Southern China – dat high salt diet
How does nasopharyngeal carcinoma present?
Painless lump in the neck
T or F: HHV-8 is necessary and sufficient to cause Kaposi’s sarcoma (KS) ?
F: Necessary but not sufficient
Human herpes virus 8 is aka ______.
KSHV
Where do KS tumors occur?
In the lining of the lymphatic system (fill lymphatic channels with blood cells –> bluish, bruised lesions)
Where is KS prevalent?
Mediterranean and sub-Saharan Africa (not sexually transmitted in these populations)
In the US, who are most of the KS patients? How is it transmitted?
AIDS patients, Sexually transmitted/via saliva (not present in semen and vaginal secretions)
Whats the typical incubation period for KS?
10 years
T or F: When symptomatic for KS, treatment in AIDS patients targets the tumor or HIV but not HHV-8.
T
Other than KS, what B cell abnormalities does HHV-8 cause?
- Primary effusion lymphoma
2. Castleman’s disease
What is primary effusion lymphoma?
KSHV+ NHL commonly found in body cavities (mean survival 2-6 months)
What is Castleman’s disease?
Lymph node tumors that are KSHV+ (not strictly cancer)
