Cytomegalovirus, EBV, Kaposi's Sarcoma- Associated Herpesvirus Flashcards
T or F. CMV, EBV, and KSHV (HHV8) are all herpes viruses
T.
All share a tropism for what?
lymphocytes
Which of the three are oncogenic viruses?
EBV and KSHV
Describe the structure of herpesviruses.
-icosahedral capsid surround by a lipid envelope containing ~12 virally derived glycoproteins
tegumnet- has important proteins for replication
Describe the genome of herpesvirus.
large, linear, double-stranded DNA ca. 150-250 kilobase pairs
CMV is largest
How do herpesviruses replicate?
genome is replicated and viruses assembled in the nucleus
T or F. In general, herpesviruses produce self-limiting infections in which the primary infection is often asymptomatic.
However, life-threatening infections or cancers can occur, especially in immune compromised hosts (neonates, AIDS, etc.)
Is the replicative cycle of herpesviruses lytic or lysogenic?
lytic in a variety of cell types
Following virus attachment, how does viral penetration occur?
by virus glycoprotein- mediated fusion of envelope and plasma membrane (pH independent)
What does the released nucleocapsid do after entering the cell?
migrates to nuclear envelope via microtubules, uncoats, and DNA enters the nucleus. Virion components act to shut off host macromolecular synthesis
Then what happens?
Programmed expression of viral genes- cascade regulation
What is the order of proteins transcribed in these viruses?
- immediate early genes
- early genes
- late genes
What do immediate early (IE) genes encode?
virus-specific transcription factors
i. use host RNA polymerase II
ii. stimulate transcription at virus early promoters
What do early genes encode?
many nonstructural proteins, enzymes
Specifically, what kinds of proteins/enzymes do early genes encode?
- DNA replication machinery, including viral DNA polymerase
- thymidine kinase (tk) which phosphorylates a variety of nucleotides besides thymidine
What do late genes encode?
structural proteins (capsids, glycoproteins)
What is late gene transcription dependent on?
IE transcription factors and genome replication
Where does virus assembly occur?
nucleus- where nucleocapsids bud first into the perinuclear space
What happens after viral assembly?
virus particles migrate to the cell surface where they are released
What is latency?
situation in which entire genomes are maintained extrachromosomally in the host indefinitely, but no virus are produced
What are the stages of latency?
a. Establishment
b. Maintenance
c. Reactivation
When does reactivation generally occur?
when there is a lapse in immunity and results in the production of virus particles and recurrent infection
How many herpesviruses are there?
8- classified on basis of their genome arrangement and latency tropism
Describe alphaherpesviruses.
neurotropic for latency,
aggressive lytic growth
What are some types of alphaherpesviruses?
a. Herpes simplex virus (HSV)-1
b. HSV-2
c. Varicella-zoster virus (VZV)
Describe betaherpesviruses.
lymphotropic for latency,
more insidious
What are some types of betaherpesviruses?
a. Cytomegalovirus (CMV)
b. Human herpesvirus-6 (HHV-6)
c. HHV-7
Describe gammaherpesviruses.
lymphotropic for latency,
more insidious
What are some types of gammaherpesviruses?
EBV
HHV-8 (Kaposi’s sarcoma)
T or F. CMV is highly contagious
F. Still, in low socioeconomic classes, infection is at 1 to 2 years of age and up to 80% of adult population is CMV positive
In higher socioeconomic classes, CMV is typically acquired after 16 years of age and only about 50% of the adult population is CMV positive
Where is CMV found in the body?
- saliva
- urine
- breast milk
- semen
- cervical secretions
- blood
- transplant organs
Who is at risk for CMV?
- neonates
- day care workers
- pregnant workers
- immunocompromised ppl
- gay men
How is CMV spread?
contact with secretions- not by aerosol
Where does CMV replicate?
epithelial cells, followed by spread to lymphoid tissue
CMV latently infects what cell types?
B-cells, T-cells, monocytes, and lymphocytes where it causes large, puffed up cells
What are the symptoms of CMV infection in utero?
- mostly asymptomatic
- retardation and deafness possible
What are the symptoms of CMV infection in adulthood?
- most asymptomatic
- mononucleosis accompanied by fever can occur
CMV is especially common in which patient population?
transplant recipients
Can result from infection by CMV+ donor or by reactivation of CMV+ recipient
CMV in transplant patients is often associated with what?
pneumonitis
How can CMV infection in transplant patients be prevented?
- prophylactic treatment with CMV Ig and ganciclovir
AIDS patients with CMV are prone to what?
retinitis
colitis
pneumonitis
How is CMV diagnosed?
- ELISA or PCR detection
- Shell vial assay in which indirect immunofluorescence is used to detect an immediate early protein after 24 h of cell culture infection
What are the treatment options for CMV?
- Ganciclovir
- Foscarnet
- Cidofovir
What is Ganciclovir?
a guanosine analog similar to acyclovir, the prototype which is used in HSV, VZV, and EBV infections
What does ganciclovir require for activity?
phosphorylation by viral kinase
Triphosphate form preferentially inhibits CMV polymerase but is more toxic to host than ACV
Side effects of ganciclovir?
neutropenia
GI bleeding
What is ganciclovir approved for?
- treatment of transplant patients
- treatment for CMV retinitis - treatment in AIDS patients
What is Foscarnet approved to treat?
- CMV retinitis in AIDS patients
same for Cidofovir
How does Foscarnet work?
Pyrophosphate analog that inhibits DNA polymerase, but does not require phosphorylation for activity
How does Cidofovir work?
it is a deoxycytidine analog that is a competitive inhibitor of CMV (and HSV) DNA polymerase, but not does require viral kinase action for activity
What is CMV possible linked to?
glioblastoma multiforme
How does Acyclovir work?
guanosine analogue that enters the body and must have 3 phosphates put on it to work. The first is added by a virally derived thymidine kinase (thus, it is specific to only infected cells), and the last two by host kinases. Once incorporated, it disrupts DNA production
T or F. Oncogenesis is the result of latency, not acute infection
T.
