MID Test II Viruses and TB Kit Delgado [email protected] Herpesviruses and Smallpox General Stuff Common Features of Herpesviruses Replicative Cycle •Morphology 1. Enveloped viral particle invades clss by utilizing receptors on the cell surface (HSV binds to members of Ig, TNF family and • Basic mode of replication VSV to mannose-6 phosphate and heparan sulfate) • Primary infection followed by latency 2. Glycoproteins (B, D, H, I) on virion – enable attachment of virus to cell (also used by the • Ubiquitous 3. Virus uncoats, DNA goes to nucleus and replicates • Ability to cause recurrent infections (reactivation of latent virus), reinfections • Transcription of viral genome and protein synthesis (cascade of gene expression), essential and luxury (with a new virus), persistent infections – 1. immediate early (IE): regulation of gene expression, DNA binding (chronic low grade virus multiplication) – 2. early (E): more transcription factors, enzymes, DNA polymerase immortalizing infections (EBV only). The other form of infection is latent, and there is little viral – 3. late (L): structural proteins gene expression, so the host cell survives. 4. Nuclecaspids are formed there, which extrude into the perinuclear space with an early envelope 5. Fuses with the RER naked nuclecaspid goes into cytosol 6. Nucleocaspid become enveloped by tegument proteins and glycoprotiens in the trans Golgi Network (TGN) 8 Human Herpesviruses, 3 categories 7. Enveloped virion incorporated into endosomes (HSV resists the acidic environment) released extracellularly • Alpha: short reproductive cycle,variable host range, latent in sensory neurons 8. virus in cell to cell spread). They are components of a new HSV2 vaccine. – Herpes simplex virus (HSV 1, 2) 9. Lytic infection cell death – Varicella- zoster virus (VZV) 10. Latency occurs when the cascade is interrupted 11. Latent infection occurs in sensory neurons • Beta: long reproductive cycle, narrow host range, latent in lymphoid cells & others – Latency associated transcripts (LATS) (salivary glands, kidney) – Minimal transcription of DNA, no translation – Cytomegalovirus (CMV) – HHV6, HHV 7 Because of cell cell spread, CMI is crucial in host response; Ab’s usually inefective (except for VSV infection. • Gamma: narrow host range; latent in lymphoid cells, associated with tumors Herpesviruses can also spread as a free enveloped particle. – Epstein Barr Virus (EBV) – Kaposi Sarcoma Virus (KSH, HHV8) • Encode targets for antiviral therapy – Thymidine kinase (TK), DNA polymerase Clinical Presentation Pathogenesis Predisposing Factors/ Likely Definitive Diagnosis Complications Treatment / Prevention Epidemiology Pathogens Genital Ulcers: Transmitted via sexual Virus can be shed by symptomatic Herpes Simplex Clinical: Associated with Acyclovir (ACV), famicylovirm, contact and asymptomatic individuals Virus 2 mostly, ulcerate leaving a primary disease: valacylovir Multiple, bilateral grouped umbilicated Invades local cell causes HSV-1 rarely shaggy ulcer Aseptic meningitis vesicles which become postular and local inflammatory Most common STD in higher (from oral lymph node Transverse coalece into large PAINFUL ulcers response socioeconomic groups genital involvement myelitis (“shaggy”) Spreads to other cells locally transmission) Sacral severe painful vulvovaginits or balantis Moves aliong sensory nervers Microscopic: radiculopathy with or without urthritis (Schawn cells) to ganglia Wright-stained or Can be pain, itching, dysuria with or without Becomes latent, reactivates Tzank stained: transmitted to urethral discharge see newborn tender inguinal lymphadenopathy multinucleated resulting in giant cell in serious organ In 1/3 of patients, symptomatic complaints: Herpes damage headache, fever, malaise, and myalgia (cytopathic involvement) Serology: Rise in anitbody titers Rule out syphilis, chancroid, LGV. 2 Baby with: Saliva transmission Usually transmitted by saliva HSV-I May lead to poor No antiviral therapy Ulcers in oral mucosa nutrition and (gingivostomatatitis) Examiners should wear gloves, dehydration of a Swollen friable gums highly infectious at this point few days Secondary infection on the thumb from sucking on it (whitlow of the finger) Baby may have fever or be irratable Although infection looks severe, it’s self limited Corneal ucers Mouth Hand eye May lead to Lesions of the conjunctival epithelium transmission scarring or (karatitis or keratoconjunctivitis) blindness Severe infection of the skin Person with underlying eczema Headache Focal Encephalitis Primary or recurrent HSV- 1 . Differential Treat with ACV if suspect disease; Fever diagnosis: TB prognosis better in children than Personality change, Most common form of focal meningitis, arbovirus, adults; early therapy is best Focal seizures, ncephalitis in USA - about 1000 enterovirus, flavivirus, Skin lesions may be present (not helpful cases of encephalitis annually mycoplasma, tumor, for diagnosis) toxoplasmosis, aneurysm Test findings: Abnormal EEG, CT, MR Diagnosis: CSF culture is usually negative, but PCR is often positive for HSV Newborn with: Perinatal HSV Usually HSV-2; Immunofluorescence Skin, mucous • Treat all newborn infants with • Usually the mother is HSV-1 in very culture, membrane possible HSV • Skin, eye, mucous membrane (40%) Perinatal HSV is usually due to asymptomatic cases PCR infection • Recurrent skin vesicles are – Skin vesicles Type 2 virus Antibody titers are untreated associated with a poorer prognosis – Good prognosis with early treatment • 95% neonatal, 5% congenital • Attack rate >10 times higher in not useful disseminated – may re- treat with ACV Untreated 75% develop disseminated maternal primary infection – May give 6 weeks of oral ACV infection infection than recurrence; attack rate about 50% CNS Infection (35%) – Fever, lethargy, seizures, abnormal CSF 1600 cases annually – 50% mortality; major sequelae if survive • Disseminated disease (25%) Hepatosplenomegaly, jaundice, hepatitis, pneumonia – 2/3 develop skin vesicles – 70% mortality Fever and malaise (prodromal symptoms) In the body VZV spreads • Varicella is likely to be severe Varicella Zoster • Culture, DFA, PCR, After primary Treatment Papulovesicular rash appears in crops on from cell-to-cell in the Immunocompromised Virus (VZV) cytology on skin infection: the trunk and then spreads to head (lack of TH1 response) rash bacterial ACV (but not as useful as for HSV and extremities (centripiltal) Varicella (Chickepox) –Can distinguish the superinfectio infections) Papules vesicles pustules crusts • VZV respiratory mucosa – Prevent or modify with pre- Oka virus from wild n, Itching blood (viremia) T cells (long formed antibodies just after type virus encephalitis, famicylovirm, valacylovir for Mild in chilren, severe in adults incubation period – 2 weeks exposure pneumonia, elderly patients with zoster from cell-cell spread) • Antibody titers, IgG congenital Years later.... – Slow spread prevents host – Treat most patients immediately –Acute serum, early in syndrome, Prevention: from being with illness Reye’s syndrome. Live, attenuated, infectious virus Painful vesicles along the course of a overwhelmed before the acyclovir –Convalescent serum, (Oka strain) sensory nerve of the head or trunk immune response • The frequency of zoster is 10- 14 days after Contraindications: pregnancy, Pain can last for weeks develops increased onset Post-herpetic immunocompromised, allergy to Postzoster neuralgia can be debilitating – Probably related to low CMI nerualgia (elderly vaccine Zoster (Shingles) response • Antibody titers, IgM and components • Latent infection in dorsal root – Likely to suffer post- herpetic –False positives and immunocompromi ganglia (DRG) neuralgia false negatives can be sed) Major complaint afterwards: mild • 6 of 68 genes (also RNA and (PHN) (also elderly) a problem rash in 5% proteins) • This vaccine is extremely safe 80% expressed during latency Rule out smallpox completely protected; 20% partial • Proteins of regulatory genes immunity. Little evidence for waning are expressed in immunity. 3 cell cytoplasm, not nucleus • Suggests regulatory proteins are blocked from normal action, leading to inhibition of cascade of gene expression preventing lytic infection from occurring (latency) • Latency is established when cell- free VZV in skin vesicles invades neurons 12-14 days afer exposure: Bioterrorist Agent (currently Smallpox virus Rule out VCV Tx Resp mucosa LN viremia eradicated around the world) (incubation similar, No known treatment Exanthema (asymptomatic) secondary difference is Strict quarantine Muculpapular rash (face mucosa trunk viremia (rash) Transmission prodome where trunks and legs) vesicles Infectious via aerosol (droplet rash starts pustules (can become confluent on face) nuclei or aerosol) (smallpox = Prev Severe looking rash gets progressively Rapid person person centrifugal), Live virus vaccine, worse Most at risk = household contacts erythmema Admin: poke with a needle (old Secondary spread 1-10 new mutliforme school) stab skin 3X for cases Swab of vesicular unvaccinated, 15X for previously High rates of transmission in fluid PCR assay at vaccinated; draw blood hospitals CDC See vacule pustule scab (if this less contagious than doesn’t happen, didn’t work) measles/varicella Lasts for a while, best for three years Patients not contagious until rash afterwards, but steadily decline begins Can see normal extra reactions (extra