Viruses - CMV, EBV, KSHV Flashcards
What is the structure of herpesvirus?
icosahedral capsid surrounded by a lipid envelope that contains about a dozen virus-encoded glycoproteins
What is the herpesvirus genome like?
large, linera, dsDNA
T or F. herpesviruses produce self-limiting infections in which the primary infection is often symptomatic?
F. primary infection is asymtomatic
Can life-threatening infections or cancers occur w/ herpesviruses?
yes, especially in immunocompromised pts.
What are examples of human herpesviruses?
CMV, EBV, HHV8, KSHV
What do herpesviruses undergo to propagate the virus?
lytic replication
What happens after virus attachment?
Virus penetrates via glycoprotein-mediated fusion of envelope and PM
What happens are the virus enters the cell?
Releases its nucleocapsid and migrates to nucleus envelope, incoats, and DNA enters nucleus.
How does the nucleocapside migrate to the nuclear envelope?
via microtubules
What is cascade regulation?
programmed expression of viral genes
What happens in the immediate early (IE) phagse?
-virus specific TFs use host RNA Pol II to stimulate transcription of early promoters
What do the early genes encode?
nonstructural proteins and enzymes
- Create DNA replication machinery, viral DNA Pol
- Thymidine kinase - phosphorylates variety of nucleotides besides thymidine
What do the late genes encode?
depend on IE transcription factors to encode structural proteins.
What happens to the newly encoded viral glycoproteins during late gene phase?
incorporated into the virus envelopes and transported to infected cell surface to cause syncytia
Where does virus assembly occur?
in the nucleus where nucleocapsids bud first into perinuclear space
T or F. All herpesvirses undergo latency?
True
What happens during latency?
genomes are maintained extrachromosomally in host but no virus are produced
What are the 3 stages of latency?
- Establishment
- Maintenance
- Reactivation
What is the genome structure of HSV like?
2 unique regions (long and short) flanked by identical inverted repeats.
What does reactivation usually occur?
when there is a lapse in immunity so virus starts making particles and causes another infection
T or F. Anyone infected w/ a herpesvirus is infected for life.
True
What are the 3 types of herpesviruses?
- Alpha (neurotropic)
- Beta (lymphotropic)
- Gamma (lymphotropic)
What are examples of beta viruses?
CMV, HHV6, HHV7
What are examples of gamma viruses?
EBV, HHV8
In low socioeconmic class, how many adults are CMV+?
80%
in higher socioeconomic classes, how many adults are CMV+?
50%
Where is CMV found?
saliva, breast milk, semen, cervical secretions, blood
Who is at risk for CMV?
neonates, day care workers, pregnant workers, immunocomprromised pts, gay men
What is the pathogenesis of CMV?
- infection via contect w/ secretions
- primary infection in epithelial cells then spreads to lymphoid tissues
- latently infects B and T cells, monocytes, and lymphocytes
When do most symptoms of CMV occur in neonates?
in utero, most are asymptomatic
What can CMV in utero result in?
retardation and deafness
T or F. Most organ translant pts get CMV infection w/ pneumonitis.
True
Can mononucleuosis occur w/ CMv?
yes
What is the prophlyactic treatment for organ transplant pts to hopefully prevent CMV infection?
Give CMV Ig and ganciclovir
T or F. When you think transplant pt, think CMV!
True
What are AIDS pts prone to with viral related stuff?
CMV retinitis, colitis, and pneumonitis
What is used for the diagnosis for CMV?
ELISA, PCR detection, and Shell Vial Assay
What is a shell vial assay?
Indirect immunofloresence used to detect an immediate early protein after 24 hr of cell culture infection
Why is a shell vial assay beneficial?
normally CMV takes 2 wks to grow so this allows for early detection
What is the treatment for CMV? Going to more efficient to less
Ganciclovir, Foscarnet, Cidofovir
What is acyclovir?
a Guansine analog w/ phosphate
What is the PK of acyclovir and MOA?
its a pro-drug, needs to have 3 phosphate groups added to it to be used by viral DNA Pol and prevent chain elongation
What is ganciclovir?
guanosine analog similar to acyclovir, prodrug
In what viral infection is acyclovir used for?
HSV, VZV, and EBV
Is acyclovir more toxic than ganciclovir?
less
What is approved for CMV retinitis in AIDS pts.?
ganciclovir, foscarnet, and cidofovir
What are side effects of ganciclovir?
neutropenia and GI tract bleeding
How does foscarnet work?
pyrophosphate analog that inhibits DNA pol but isn’t a pro-drug.
How does cidofovir work?
deoxycytidine analog, competitive inhibitors of CMV DNA Pol
Why can’t these antivirals cure herpes or treat cancers caused by these viruses?
They inhibit virus replication to limit infection, but these viruses will undergo latency so there is no virus replication going on
Tell me about EBV infection is different socieconomic groups?
low setting – at early age
higher setting – adolescence and adulthood
How much of the adult population has an Ab to EBV?
90-95%
What can EBV cause in immunocompromised hosts?
oral hairy leukoplakia
What are 2 cancers that ENV are associted w/?
Burkitt’s lymphoma and nasopharyngeal carcinoma
How is EBV spread?
through saliva – kissing
what is the incubation period for EBV?
4-7 weeks
where is the initial replication of EBV after infection?
oropharyngeal epithelium
Where can EBV spread to?
lymphocytes and then liver and spleen
Where will EBV remain latent?
throat epithelium and B cells
How long does oral shedding of EBV last?
week or even months
T or F. Most EBV infections are symptomatic.
F
What is symptoms of infection mononucleosis?
sore throat, fever for one to two wks, malaise, lymphadenopathy
What is the diagnosis of EBV based on?
symptoms and presence of at least 50% atypical large lymphocytes w/ lobulated nuclei
What is the role of the large lymphocytes in mono?
T cells responding to the infection, not the infected B cells
What are important Antigenic Markers of EBV?
- EBNA
- VCA
- EA
When does one see EBNA? (EBV nuclear antigens)
early in primary infection, it maintains genome replication in dividing B cells
What does anti-VCA IgM indicate?
primary infection
What does anti-VCA IgG indicate?
- w/out anti- EBNA indicates primary infection
- w/ anti-ENBA indicates past infection
When is EA seen? (early antigen)
detected in cells that don’t produce virus
How do you diagnose EBV infection?
Monospot test, aka Heterophile Antibodies
What do the Abs agglutinate w/ monospot test?
sheep red blood cells
What is the treatment for mono?
supportive, tell athletes to not to do physical activity due to enlarged spleen.
What is PTLD?
uncontrolled proliferation of B cells due to their transformation by EBV and absence of CTLS to control them
What is the treatment for PTLD?
stop immunosuppression, monitor for rejection and acyclovir is not useful b/c infection is latent
When is the highest risk for PTLD?
in seronegative EBV transplant recipients in the 1st year
What is Burkitt’s Lymphoma?
neoplasm of B cells that affect bones of the jaw, endemic in central Africa and New Guinea
What are the 3 associated factors w/ Burkitt’s Lymphoma?
- early EBV infection leading to latency
- activation of c-myc
- malaria
What does early detection of Burkitt’s lymphoma allow?
cure rate of 80%
How many people have EBV genomes in Burkitt’s outside Africa?
20%
What is nasopharyngeal carcinoma?
neoplasm of epithelial cells
Where is nasopharyneal carcinoma common?
southern china– high salt diet likely cofactor
What is the initial presentation of nasopharyngeal carcinoma?
painless lump in the neck
How many people survive ten years if they have nasopharyngeal carcinoma?
60%
What can cause Kaposi’s sarcoma?
HHV8 is necessary but not sufficient
What happens w/ the B cells and the endothelial latency tropism w/ HHV8?
KS tumors are in lining of lymphatic system, the lymphatic channels fill w/ blood cells –> causes bluish, bruised appearance of lesion
In US, who usually has KS?
AIDS patients
How does HHV8 spread?
- sexually-transmitted but virus is absent from semen and vaginal secretions, it’s found in saliva
What is the incubation of HHV8 before onset of KS?
10 years
is HHV8 symptomatic in AIDS and in non-AIDS?
no, asymptomatic
When will HHV8 infection by symptomatic?
- must be accompanied by loss of immune system so common in old age and AIDS in gay populations
When symptomatic, what is the treatment of HHV8 in AIDS?
there is no treatment for HHV8 but instead aim is to treat AIDS patients for tumor specific or targets of HIV
What other cancers can HHV8 cause?
- primary effusion lymphoma
2. multicentric Castleman’s diseas
What is primary effusion lymphoma?
NHL B cell, found in body cavities, mean survival time 2-6 months
What is multicentric Castleman’s disease?
lymph node tumors, not strictly a cancer (not metastatic)
T or F. KSHV is found in virtually all tumors of HIV+ pts.
T
