Herpes Viruses Flashcards
(28 cards)
Which herpes virus is VZV?
HHV-3
HHV 4-8
Name of disease
Which cells are infected?
- Epstein-Barr Virus (HHV-4). Resting B cells.
- Human Cytomegalovirus (HHV-5). Monocytes.
- Human Herpes virus 6 (HHV-6). CD4 T cells. 95% seropositive by age 5.
- Human Herpes virus 7 (HHV-7). CD4 T cells. 95% seropositive by age 12
- Kaposi’s Sarcoma Associated Herpes Virus (HHV-8). Possible B cells. Sexually transmitted.
What does a tegument do?
Space b/w capsid and envelope, which allows viruses to take over host cell machinery and initiate infection. Some tegument proteins act as enhancers that promote early gene expression. Others inhibit effector functions induced by IFN or initiate host shutoff.
Neurotropic viruses (alpha)
Become latent, w/ genome circularizing / interacting w/ histones to form chromatin-like structure. These cells do NOT divide, so no viral proteins need to be made in order to replicate during the latent phase.
Lymphotropic viruses (beta / gamma) 3 viral protection methods
These cells DO divide, so 5 proteins must be made during latency in order for viral genome to replicate. These proteins may be targets for the immune system, so virus has protection methods:
• Viral cytokines mimic immunosuppressive cytokines IL-4 and IL-10
• Virus encodes proteins that act as decoy receptors for host cytokines
• Viral proteins prevent degradation of genome to prevent presentation by APCs
Where is chickenpox rash localized to?
Mainly on trunk / limbs
Which viruses integrate into genome during latency? Which ones do not?
Only HHV6 / 7 integrate during latency
The rest do not.
Reactivation vs recrudescence
- Reactivation – asymptomatic shedding occurs in 60% of pxs w/ genital herpes. Often due to rapid events of microshedding (12 hrs). Disease may spread during this time.
- Recrudescence – symptoms reappear (cold sores, shingles, etc). CD8 cells may release IFNg to try to stop infection during the lytic phase.
Skin appearance of HSV 1 / 2
Fluid filled vesicles form and then pop → open wet ulcers. Usually do NOT scab.
Which herpes virus causes encephalitis?
Sxs
HSV1
Leading cause of sporadic encephalitis in US. May progress from malaise to confusion to coma. Necrotic lesions may form on temporal lobe. Critical to start antivirals right away if suspected, even before diagnosis.
Which herpes virus cases meningitis?
HSV2. Usually self limiting
5 reactivation triggers for HSV 1 / 2
- Stress
- UV light (use sunscreen on spots of cold sore)
- Steroid hormones
- Trauma to latently infected ganglia (including surgery)
- Decreased immune function
HSV latent gene expression
Only one gene is expressed during latent period: latency associate transcript. Persists as RNA intron, no protein made. Blocks apoptosis of neurons. RNA is not antigenic so immune system does not detect anything
Diagnosing HSV 1 / 2
Usually made by appearance of lesions.
PCR much more than culture.
Tzanck stain looks for syncytium.
PCR on CSF is gold standard for encephalitis. Neuro sxs such as lethargy, confusion, and inability to sit upright are clues for encephalitis.
VZV
Transmission
Rash
Treatment
- Transmitted by aerosol and contact w/ fluids from vesicles. Causes disseminated infection.
- Rash is vesicular, not macular. Looks similar to herpes but ulcers DO scab over. Mainly affects face and trunk, sparing the limbs.
- Tx rash w/ calamine lotion or baking soda baths
Zoster / Shingles
Sxs
Recurrence?
Vaccine
- Ulcerating rash is very painful. May last up to 1 month.
- Post-herpetic neuralgia may last many months after rash is gone. Very painful and can be refractory to analgesics. Antivirals reduce pain.
- Usually only have one outbreak in a lifetime.
- VZV vaccine recommended in pxs over age 50, even if you had the disease as a child.
hCMV primary infection
2 main diseases w/ sxs
- 1) Heterophile negative mononucleosis – Most common disease caused by HCMV. Sxs include fever, malaise, sore throat, lymphadenopathy, and hepatitis. Self limiting.
- 2) Congenital cytomegalic inclusion disease:
- Jaundice, hepatosplenomegaly, microcephaly, petechial rash, mental retardation, chorioretinitis
- Leading cause of birth defects. Greatest risk is primary infection in seronegative pregnant mother. Sxs in child are more severe if earlier in pregnancy. May be lethal to fetus.
hCMV reactivation
Population
2 manifestations
- Does not occur in immunocompetent people but causes problems in immunosuppressed pxs, such as those w/ organ transplants.
- Hepatitis may occur in liver transplant pxs
- CMV retinitis occurs in AIDS pxs –> blindness
Diagnosing hCMV
- “Owl eye” cells seen in saliva and tissues
- Immunostaining for viral antigens. Immediate Early (IE) antigens give fastest results
- PCR
- Culture not done due to slow growth
Treating hCMV
Antivirals only used for serious infections, such as bone marrow transplant pxs
EBV primary infection
2 main diseases
Heterophile (+) mononucleosis
Hepatitis
Mono
Sxs
Diagnosis
- Fever, sore throat, lymphadenopathy, severe malaise, tonsular exudate, petechial spots on palate, heterophile Abs. Not lethal.
- Diagnose w/ monospot test and viral-specific antigens.
- People w/ heterophile make Abs against foreign red blood cell
EBV reactivation
Population
2 manifestations
- No disease in immunocompetent (similar to HCMV). Immunosuppressed pxs:
- Poly / monoclonal lymphoproliferative syndromes (lymphomas), commonly seen in AIDS pxs
- Oral hairy leukoplakia in AIDS pxs as well – big white scaly patches on tongue
EBV associated cancer
Mechanism
3 types of cancer w/ location, population, and sxs
- Mechanism – If B cell is infected when the rag gene is being expressed, the virus prolongs this expression. Rag catalyzes rearrangements of Ig gene segments (VDJ joining), so prolonged activation → chromosomal translocations → overexpression of C myc (proto-oncogene) → transformation
- Burkitt’s Lymphoma
- Found in central Africa
- Tumors show up in children age 6-15. Usually infected before age 1.
- Solid tumors of jaw and long bones
- Some association with Malaria. Endemic maps overlap. Possible that malaria may cause immunosuppression → cancer.
- Nasopharyngeal Carcinoma – Endemic in Southern China. Usually affects adults. Does not involve B cells. EBV acts as co-factor.
- US – American Burkitt’s and other solid B cell tumors (lymphomas)
