3.26 RYAN CMV, EBV, and KSHV Flashcards
CMV Pathogenesis
- Not highly contagious
- direct contact with secretions, not by aerosol, primary replication in epithelial cells, followed by spread to lymphoid tissue
- CMV latently infects B-Cells, T-Cells, monocytes and lymphocytes where it causes large, puffed up cells
CMV symptoms
- 80% of adult pop is CMV+
- Neonatal infections can occur un utero; most are asymptomatic, cause result in retardation and deafness
- Most adult infections are also asymptomatic, but mononucleosis accompanied by fever can occur
Immunocompromised
- At high risk
- most organ transplant patients get CMV infection with pneumonitis representing the most life-threatening aspect
- -infect from CMV+ donor or by reactivation of CMV+ recipient
- -prophylactic treatment with CMV ig and ganciclovir (promising)
- AIDS patients are prone to CMV retinitis, colitis and pneumonitis
Diagnosis
-ELISA or PCR detection, shell vial assay
CMV Treatment
Ganciclovir: requires phos by viral kinase for activity, side effects: neutropenia and GI tract bleeding
Epstein-Barr Virus (EBV)
- Adolescence and early adults get mononucleosis
- 90 to 95% of adult pop contains ab to EBV
- can cuase oral hairy leukoplakia in immunocomp
- Posttransplant lymphoproliferative disease (PTLD) in some transplant pts
- associated with Burkitt’s lymphoma and nasopharyngeal carcinoma
EBV pathogenesis
- Spread through saliva
- incubation period 4-7 weeks
- initial replication in oropharyngeal epithelium
- Sperad to lymphocytes and then liver and spleen
- EBV remains latent in throat epithelium and B-cells
- Oral shedding of virus occurs for many weeks
EBV symptoms
Most infections are asymptomatic
- Infectious mononucleosis: sore throat, fever 1-2 weeks, malaise, lymphadenopathy
- Recovery is uneventful
Diagnosis
- at least 50% atypical, large lymphocytes with lobulated nuclei
- diagnosis usually made off symptoms
- Large lymphocytes are T-cells responding to infection, not infected B-cells***
- Monospot test test for EA (early antigen)
Antigenic markers
EBNA-EBV nuclear antigens arise early in primary infection, EBNA1 maintains genome replication in dividing b-cells, conversion to anti-EBNA IgG indicates resolution of primary infection
- VCA: viral capsid antigen,
- -anti-VCA IgM: primary infection
- -anti-VCA IgG w/o anti-EBNA: primary infection
- -antiVCA IgG w/ anti EBNA IgG: past infection
EBV and neoplasms
PTLD: uncontrolled prolifertion of B cells, highest risk in seroneg transplant recipients
–treatment: stop immunosuppression (be careful, watch for rejection)
BURKITT’S: neoplasm of B-cells that affects bones of the jaw (africa and new guinea)
–associated w/ 3 factors: (1) early EBV infection leading to latency (2) activation of c-myc (3) malaria: suppresses typical immune response
NASOPHARYNGEAL CARCINOMA: epithelial cells, ass with EBV worldwide, high frequency in souther CHINA (high salt diet), at best 60% pts survive 10 yrs
QUICK THINK: compare and contrast CMV and EBV
Both can cuase mono and are latent in B cells. Both can cause Post-transplant complications, but presentation is diff.
-CMV is sexually transmitted and a source of congenital infection
-CMV is always heterophile AB neg
(neg mono spot test)
-EBV is a known oncogenic virus
Human herpesvirus-8 (KSHV)
- could cause kaposi’s sarcoma
- B-cell and endothelial latency tropism
- –lining of the lymphatic system, lymph channels fill with blood cells: bluish bruised appearance
KS pts in US
They are AIDS patients
- sexually trans-but no virus in semen and vaginal secretions
- present in saliva: STD not understood
- 10 yr incubation period b/f onset of KS: may be mild, can be life-threatening in immunocomp
HHV-8 B cell abnormalities
Primary effusion lymphoma: non-hodgkin B-cell lymphoma, commonly found in body cavities, mean survival tiem 2-6 months, KSHV found in virtually all tumors of HIV+ pts
CASTLEMAN’S DISEASE: lymph node tumors, not strictly cancer, KSHV found in virtually all tumors of HIV+ pts (nonmetastic)
Herpes overview
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
-Undergo lytic replication
Lytic Replication
-Penetration via glycoproten-mediatd fusion of envelope and plasma membrane
-Nucleocapsid goes to nuclear envelope (microtubules) and DNA enters nucleus
-Immediate Early (IE) genes are virus-specific transcription factors: use host RNA poly II and stimulate transcription at virus early promoter
-Early genes: nonstructural proteins, enzymes: DNA rep machinery (viral DNA poly) and thymidine kinase which phos a variety of nucleotides besides thymidine
Late genes: dependent on IE transcription factors plus genome replication for expression: encode structural proteins, viral glycoproteins are incorporated into virus envelopes and also transported to infected cell surface where they can cause syncytia formation
-Virus assembly occurs in the nucleus: nucleocapsids bud first into the perinuclear space
-Virus particles migrate to the cell surface where they are released
Alt to lytic infection
All herpesviruses also undergo latency in which the entire genome are maintained extrachromosomally in the host indef, but no virus are produced 3 stages: (1) establishment, (2) maintenance (3) reactivation
