CMV, EBV, KSHV (HHV-8) Flashcards
What type of virus are CMV, EBV, and KSHV?
• What do they share a common tropism for?
• Which of these cause cancer?
All are herpes Viruses
- All share tropism for Lymphocytes
- EBV and KSHV are oncogenic
Describe the following structural features of the Herpes virus? • Genome Structure • Capsid style • Enveloped • Where does virus assembly take place?
Genome:
• Linear dsDNA (150-250 kbp)
Capsid:
• Icosahedral Capsid
• Enveloped
REPLICATION AND ASSEMBLY TAKE PLACE INSIDE THE HOST CELL NUCLEUS
Which of the herpes viruses is the largest?
CMV is the largest
What is the Tegument?
• what is found here?
Tegument:
• Found Between the envelope and capsid
What does it contain:
•number of proteins needed to infect the cell and shut down host cell synthesis of normal proteins to produce viral proteins
Which of the following are Beta and which are Gamma herpes viruses?
Beta = CMV
Gamma = EBV, HHV-8 (KSHV)
**Note: EBV and HHV-8 can cause cancers
What is unique about the structure of the herpes virus linear genome structure for:
• CMV
• EBV
• Line is divided into Long Segement and Short segment
CMV:
• Flanking each of these segments is two pairs of genes that are the same but run in opposite directions
EBC:
• Internal Repeats separate Long and short segment
T or F: herpes viruses can take part in a lytic cycle OR stay in a latent phase.
TRUE, the latent phase is what makes herpes life-long
Describe the Steps in the Lytic Cycle for Herpes viruses.
ENVELOPE fuses with cell and NUCLEOCAPSID rides microtubules to host nuc.
Immediate Early Phase
• Early Transciption Factors - redirect host RNA pols. to make viral genes
Early Phase
• HERPES own DNA pols replicates Genome
Late Phase
• Packing into capsid occurs in the nucleus
Assembled Virus Buds from the Nucleus and out of the cell
What events occur if the herpes virus decides to undergo a latent phase rather than lytic?
- NO VIRAL PARTICLES are PRODUCED
- Entire Genome is Maintained Extrachromosomally
- FEW viral genes are expressed
What are the 3 phases of latency?
• What causes the final stage?
Establishment
Maintenance
Reactivation - Due to a Loss in Host Immune Response
T or F: latency in herpes viruses causes the infection to be LIFE-LONG
True
What 4 drugs are most often used to treat Herpes viruses?
• Which are 1st line and which are 2nd line?
4 Drugs:
1st line (pro-drugs)
• Acyclovir
• Ganciclovir
2nd line (not pro-drugs) • Foscarnet • Cidofovir
Acyclovir
MOA
- PRODRUG is phosphorylated FIRST by HERPES Thymidine Kinase (two more phosphorylations occur by host kinases)
- Is Preferentially used by HERPES DNA pols.
(thymidine analogue)
Which of the herpes drugs is most often used to treat CMV infections?
Ganciclovir
Foscarnet
MOA
- Blocks Pyrophosphate Release (aka cleaving of the P-P bond)
- NOT a prodrug and DOES NOT REQUIRE activation
Cidofovir
MOA
Cytidine analogue (doesn’t need to be activated)
Why can’t anti-herpetic drugs cure herpes?
They ONLY affect herpes in its active Relicating state and have no effect on the lytic state
T or F: CMV is not highly contagious , that’s why rates of CMV infection are generally very low in society.
FALSE, while it IS true that CMV is not highly infectious is it however VERY PREVALENT with 50-80% of adults being affected.
T or F: Like HSV-1 both CMV and EBV are sexually transmitted.
False, CMV IS sexually transmitted while EBV is NOT (despite its reputation)
What is the PRIMARY (first) site of replication for CMV?
• Secondary?
• Latency?
Primary:
Epithelial Cells
Secondary:
• Spreads through Lymphoid Tissue
Latency:
• Hangs out in B and T cells and Monocytes
Compare and contrast Childhood infections of CMV with those that occur as an adult?
Childhood:
• Mostly Asymptomatic
Adulthood:
• can result in mononucleosis with fever
How does CMV affect Neonates?
• How many are affected in utero?
- In utero CMV in 1% of U.S. births
* Asymptomatic 90% of the time but CAN cause Deafness and Mental Retardation
What groups of people are at the highest risk of getting CMV infection?
- Immunocompromised (TRANSPLANT patients)
- Day Care Workers
- Pregnant Workers
- Gay Men
When you think transplant patient, think CMV!
When you think transplant patient, think CMV!
T or F: most transplant patients will develop a CMV infection.
True, but not all will cause disease
How does CMV exposure occur in transplant patients?
• How would you treat someone who is at high risk for CMV exposure during transplant?
- CMV+ organ is recieved OR
- REACTIVATION of latent CMV in CMV+ pt.
• HIGH RISK (seropositive) pts. are given PROphylactic Ganciclovir and CMV Ig
How do you diagnose and treat someone with a CMV infection?
• 1st and 2nd line treatment
Dx:
• Detection of VERY Large Lymphocytes
• ELISA, PCR, Shell Vial Assay
Treatment:
1st line
• Ganciclovir
2nd line
• Foscarnet
• Cidofovir
What is a shell vial assay?
• Uses Antibody to detect Immediate Early Proteins
this is quicker because you don’t have to wait for the virus to completely replicate
What two cancers can be caused by EBV?
- Burkitt’s Lymphoma
* Nasopharyngeal Carcinoma
Which causes hairy leukoplakia of the tongue: EBV or CMV?
EBV
Where is the primary site of replication for EBV?
• Secondary?
• Tertiary?
Primary - Epithelium
Secondary - Lymph Nodes
Tertiary - Liver and Spleen
Why do people often not know they are infected with EBV and thus spread it to other people?
EBV remains latent in throat epithelia and B cells and there can be oral shedding for weeks
What some of the key symptoms of Infectious Mononucleosis (EBV) infection?
- Sore Throat
- Fever 1-2 wks
- Malaise
- Lymphadenopathy
- Uneventful Recovery
What patients present with hairy leukoplakia?
• what causes it?
AIDS patients are really the only people this is seen in
• Caused by EBV
How is EBV typically diagnosed?
- Symptoms
- Greater than 50% atypical, LARGE lymphocytes
- Monospot test (specific but not sensitive)
- EBNA and VCA antigens
How does the monospot test work?
• How good is this test at catching EBV?
HETEROPHILE antibodies agglutinate Sheep RBCs
• on 1/2 of people infected with EBV ever produce ant-sheep antibody
*What are EBNA and VCA?
EBNA (EB Nuclear Antigens)
• Immediate Early proteins that Assist in transcription and Genome Replication
VCA (Virus Capsid Antigen)
• Produced during Lytic Replication
*How are EBNA and VCA used to stage an EBV infection?
Anti-VCA rises before anti-EBNA therefore
Primary Infection
• Anti-VCA+ and anti-EBNA -
Prior Infection
• Anti-VCA+ and anti-EBNA+
*What is posttransplant lymphoproliferative disease (PTLD)?
• which transplant pts. are at highest risk?
• What virus causes this?
• How do we treat?
PTLD
• B Cell lymphoma in Transplant Patients
Highest Risk:
• Patients in the 1st year of treatment who are SERONEGATIVE for EBV
Treatment:
• Stop Immunosuppression
*Who typically gets Burkitt’s lymphoma?
• factors that play a role in getting the disease?
Young Children in Central Africa
Factors:
• Early EBV infection - causes immortalization leading to more replication and more mutations
- c-MYC gets activated as a result of mutations
- Superimposed Malaria infection suppresses normal immune response to EBV
How curable is Burkitt’s lymphoma?
80% cure rate in cases that are detected early
Which is more closely associated with EBV, Nasopharyngeal Carcinoma or Burkitts Lymphoma?
There is almost 100% association of Nasopharyngeal Carcinoma with EBV.
Where is nasopharyngeal carcinoma most prevalent?
Southern China - thought to be tied in to high consumption of Nitrosamines and Grilled Fish in these areas
Compare and Constrast EBV to CMV in terms of: • Cell in which it remains Latent • Effect on Transplant Patients • Transmission • Mono-spot test • Oncogenesis
Latency:
• Occurs in B cells for Both
Effect on Transplant Patients:
• CMV - PNEUMONIA 1-4 months After transplant
• EBV - B cell lymphoma
Transmission:
Both transmit through fluids (enveloped virus)
• CMV - sexually transmitted
• EBV - only transmitted via Saliva
Monospot:
• CMV - ALWAYS negativ
• EBV - sometimes positive
Oncogenesis:
• only EBV causes cancer
What are some diseases caused by HHV-8 (KSHV)?
- Kaposi’s Sarcoma
- Primary Effusion Lymphoma
- Castleman’s disease
