Micro/CMV,EBV,KSHV

Question 1

CMV, EBV, and KSHV are latent in these types of cells

Answer 1

lymphocytes

Question 2

Describe CMV,EBV,KSHV genome and structure

Answer 2

large, linear, dsDNA; icosahedral enveloped

Question 3

CMV is this type of herpes virus

Answer 3

Betaherpesvirus

Question 4

EBV is this type of herpesvirus

Answer 4

Gammaherpesvirus

Question 5

Describe the genomic structure of HSV-1

Answer 5

Two unique regions (long and short) encoding viral gene products, each flanked by inverted repeat sequences

Question 6

Describe the genomic structure of EBV

Answer 6

Multiple repeat region with amplified gene sequences; NO inverted repeats

Question 7

Describe the genomic structure of CMV

Answer 7

Similar to HSV-1

Question 8

Describe the lytic cycle

Answer 8

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.

Question 9

Describe the order of protein production when a herpesvirus infects a cell and what types of proteins are in each stage

Answer 9

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)

Question 10

Describe the three phases of latency

Answer 10

Establishment; Maintenance; Reactivation

Question 11

Are herpesviruses maintained in or out of the chromosome?

Answer 11

External to

Question 12

Which viruses can cause mono?

Answer 12

CMV and EBV

Question 13

How is CMV spread?

Answer 13

Through direct contact with secretions (saliva, urine, milk, semen, blood)
Considered an STI

Question 14

Who is at risk for CMV infection?

Answer 14

Neonates, daycare workers, pregos, immunocompromised (AIDS, transplant), gay men

Question 15

Can CMV be spread through aerosol?

Answer 15

NO

Question 16

In utero infections with CMV may cause these defects

Answer 16

MR, deafness

Question 17

Who is most at risk for CMV?

Answer 17

Transplant patients!

Question 18

What is a common infection in immunocompromised patients infected with CMV?

Answer 18

Pneumonitis

Question 19

How does pneuominitis occur in transplant patients with CMV?

Answer 19

Either through a positive donor or reactivated latent CMV

Question 20

How do you prevent transplant patients from getting CMV infections?

Answer 20

Ig and ganciclovir

Question 21

What does CMV cause in AIDs patients?

Answer 21

Retinitis, pneumonitis

Question 22

How do you diagnose CMV infection?

Answer 22

Very large-looking lymphocytes; ELISA/PCR to detect DNA amplification; shell vial assay

Question 23

Explain the shell vial assay

Answer 23

Infect a monolayer of cells with potential CMV-infected source; after 12-18 hrs, check for antibody presence using IF

Question 24

When does pneumonitis usually present in transplant patients with CMV infection?

Answer 24

Several months after transplant

Question 25

What is the drug of choice for CMV treatment?

Answer 25

Gangciclovir

Question 26

What is the second line of therapy for CMV infections?

Answer 26

Acyclovir and foscarnet

Question 27

What treatment is best for AIDs patients with pneumonitis due to CMV?

Answer 27

Foscarnet

Question 28

What is unique about Foscarnet and Cidofovir compared to Ganciclovir?

Answer 28

They don't require activation through kinase phosphorylation

Question 29

Describe Acyclovir MOA

Answer 29

Pro-drug guanosine analog requiring 3 phosphorylation events; first must be by viral kinase

Question 30

What percent of the adult population is seropositive for EBV?

Answer 30

~95%

Question 31

Which viruses causes hairy leukoplakia?

Answer 31

EBV

Question 32

Hairy leukoplakia is often a complication of what infection?

Answer 32

AIDS

Question 33

PTLD is caused by which virus?

Answer 33

EBV

Question 34

Describe the pathogenesis of EBV infection

Answer 34

Spread through saliva Incubation period several weeks Starts in oropharynx, then spleen Oral shedding for many weeks

Question 35

What are the symptoms of mono?

Answer 35

Sore throat, fever 1-2 wks, malaise, lymphadenopathy

Question 36

How do you diagnose mono?

Answer 36

50% atypical, large lymphocytes with lobulated nuclei and/or use Monospot (heterophile antibody) test

Question 37

How does Monospot work?

Answer 37

Test for agglutination against sheep RBCs; positive test indicates EBV infection mono and not CMV mono

Question 38

EBV can cause which neoplasms?

Answer 38

PTLD, Burkitt's, and nasopharyngeal carcinoma

Question 39

Who has the highest risk of contracting PTLD?

Answer 39

Seronegative EBV transplant recipients in the first year

Question 40

How do you treat PTLD?

Answer 40

Stop the immunosuppression and monitor for rejection

Question 41

Why doesn't ACV work in PTLD?

Answer 41

Infection is latent; ACV requires replication to work

Question 42

Describe Burkitt's lymphpoma and contributing factors

Answer 42

B-cell lymphoma affecting jaw (Africa); Associated with 1) Early EBV infection -> immort B cells 2) C-Myc activation to Ig promoter 3) Malaria

Question 43

Compare Burkitt's and nasopharyngeal carcinoma in terms of EBV-related pathogenesis

Answer 43

NPC is 100% caused by EBV, whereas Burkitt's has other causes

Question 44

What is the relationship between KSHV and Kaposi's sarcoma

Answer 44

Necessary but not sufficient; need immunocompromise; KSHV DNA recovered from >95% of tumors

Question 45

How is KSHV spread and who is at risk?

Answer 45

AIDS patients at risk; STI spread but is not present in semen or vaginal secretions

Question 46

What does Kaposi's look like?

Answer 46

Bluish, blue appearing lesions

Question 47

Where does KSHV become latent?

Answer 47

B cells and endothelium

Question 48

Beside's Kaposi's, KSHV/HHV-8 causes what B cell abnormalities?

Answer 48

Primary effusion lymphoma (NHL; body cavities; mean survival 2-6 mo); Castleman's disease (nonmetastatic lymph node tumors)