Micro/CMV,EBV,KSHV Flashcards
CMV, EBV, and KSHV are latent in these types of cells
lymphocytes
Describe CMV,EBV,KSHV genome and structure
large, linear, dsDNA; icosahedral enveloped
CMV is this type of herpes virus
Betaherpesvirus
EBV is this type of herpesvirus
Gammaherpesvirus
Describe the genomic structure of HSV-1
Two unique regions (long and short) encoding viral gene products, each flanked by inverted repeat sequences
Describe the genomic structure of EBV
Multiple repeat region with amplified gene sequences; NO inverted repeats
Describe the genomic structure of CMV
Similar to HSV-1
Describe the lytic cycle
Initial infection occurs when virus attaches to heparin sulfate proteoglycans. It then binds more tightly another receptor.
Viral encelope fuses directly with the plasma membrane in a pH-indep event, releasing nucleocapsid inside the cell.
Nucleocapsid migrates along microtubules to nucleus where genomic DNA is released.
Describe the order of protein production when a herpesvirus infects a cell and what types of proteins are in each stage
1) Immediate early genes - transcription factors; use host RNA pol II
2) Early genes - nonstructural proteins; enzymes (make DNA pol; need IEs)
3) Late genes - structural (need IEs)
Describe the three phases of latency
Establishment; Maintenance; Reactivation
Are herpesviruses maintained in or out of the chromosome?
External to
Which viruses can cause mono?
CMV and EBV
How is CMV spread?
Through direct contact with secretions (saliva, urine, milk, semen, blood)
Considered an STI
Who is at risk for CMV infection?
Neonates, daycare workers, pregos, immunocompromised (AIDS, transplant), gay men
Can CMV be spread through aerosol?
NO
In utero infections with CMV may cause these defects
MR, deafness
Who is most at risk for CMV?
Transplant patients!
What is a common infection in immunocompromised patients infected with CMV?
Pneumonitis
How does pneuominitis occur in transplant patients with CMV?
Either through a positive donor or reactivated latent CMV
How do you prevent transplant patients from getting CMV infections?
Ig and ganciclovir
What does CMV cause in AIDs patients?
Retinitis, pneumonitis
How do you diagnose CMV infection?
Very large-looking lymphocytes; ELISA/PCR to detect DNA amplification; shell vial assay
Explain the shell vial assay
Infect a monolayer of cells with potential CMV-infected source; after 12-18 hrs, check for antibody presence using IF
When does pneumonitis usually present in transplant patients with CMV infection?
Several months after transplant
What is the drug of choice for CMV treatment?
Gangciclovir
What is the second line of therapy for CMV infections?
Acyclovir and foscarnet
What treatment is best for AIDs patients with pneumonitis due to CMV?
Foscarnet
What is unique about Foscarnet and Cidofovir compared to Ganciclovir?
They don’t require activation through kinase phosphorylation
Describe Acyclovir MOA
Pro-drug guanosine analog requiring 3 phosphorylation events; first must be by viral kinase
What percent of the adult population is seropositive for EBV?
~95%
Which viruses causes hairy leukoplakia?
EBV
Hairy leukoplakia is often a complication of what infection?
AIDS
PTLD is caused by which virus?
EBV
Describe the pathogenesis of EBV infection
Spread through saliva
Incubation period several weeks
Starts in oropharynx, then spleen
Oral shedding for many weeks
What are the symptoms of mono?
Sore throat, fever 1-2 wks, malaise, lymphadenopathy
How do you diagnose mono?
50% atypical, large lymphocytes with lobulated nuclei
and/or
use Monospot (heterophile antibody) test
How does Monospot work?
Test for agglutination against sheep RBCs; positive test indicates EBV infection mono and not CMV mono
EBV can cause which neoplasms?
PTLD, Burkitt’s, and nasopharyngeal carcinoma
Who has the highest risk of contracting PTLD?
Seronegative EBV transplant recipients in the first year
How do you treat PTLD?
Stop the immunosuppression and monitor for rejection
Why doesn’t ACV work in PTLD?
Infection is latent; ACV requires replication to work
Describe Burkitt’s lymphpoma and contributing factors
B-cell lymphoma affecting jaw (Africa); Associated with
1) Early EBV infection -> immort B cells
2) C-Myc activation to Ig promoter
3) Malaria
Compare Burkitt’s and nasopharyngeal carcinoma in terms of EBV-related pathogenesis
NPC is 100% caused by EBV, whereas Burkitt’s has other causes
What is the relationship between KSHV and Kaposi’s sarcoma
Necessary but not sufficient; need immunocompromise; KSHV DNA recovered from >95% of tumors
How is KSHV spread and who is at risk?
AIDS patients at risk; STI spread but is not present in semen or vaginal secretions
What does Kaposi’s look like?
Bluish, blue appearing lesions
Where does KSHV become latent?
B cells and endothelium
Beside’s Kaposi’s, KSHV/HHV-8 causes what B cell abnormalities?
Primary effusion lymphoma (NHL; body cavities; mean survival 2-6 mo); Castleman’s disease (nonmetastatic lymph node tumors)
