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USMLE (Fach) / Virology (Lektion)
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- Deltavirus Enveloped, Θ single-stranded and circular RNA HDV is a "defective" virus that requires the presence of HBV (for HbSAg) to replicate.
- Segmented viruses All are RNA viruses. - Orthomyxoviruses- Arenaviruses- Bunyaviruses- Reoviruses
- Extrahepatic manifestations of hepatitis B and C Hepatitis B:- Hematologic: Aplastic anemia- Renal: Membranous GN > membranoproliferative GN- Vascular: Polyarteritis nodosa Hepatitis C:- Hematologic: Essential mixed cryoglobulinemia, ↑ risk B-cell NHL, ITP, autoimmune hemolytic anemia- Renal: Membranoproliferative GN > membranous GN- Vascular: Leukocytoclastic vasculitis- Dermatologic: Lichen planus, sporadic porphyria cutanea tarda- Endocrine: ↑ risk of diabetes mellitus, autoimmune hypothyroidism
- Dengue fever Flavivirus (enveloped, ⊕ ssRNA)- Transmitted by Aedes aegypti mosquito- Distribution: tropical regions worldwide, particularly Asia (eg, Thailand) Classic dengue fever:- Flu-like febrile illness with marked myalgias & joint pains ("break-bone fever")- Severe headache and retro-orbital pain- Maculopapular, measles-like rash ("white islands in sea of red")- Generalized lymphadenopathy Dengue hemorrhagic fever: - More frequent in individuals who experience a repeat infection with a second serotype.- Abdominal pain, vomiting- Changes in mental status- Hemorrhagic manifestations (eg, petechiae, epistaxis), spontaneous bleeding → shock- Increased vascular permeability → signs of pleural effusion and/or ascites- Dengue shock syndrome (DHF + shock) - Leukopenia, thrombocytopenia- Serology- Positive tourniquet test (petechiae after sphygomomanometer cuff inflation for 5 minutes) Management: Supportive care
- West Nile virus Flavivirus (enveloped ⊕ ssRNA) Clinical syndrome:- West Nile fever: fever, headache, rash (maculopapular/morbilliform) on back and chest- Neuroinvasive: meningitis, encephalitis, acute asymmetric flaccid paralysis, Parkinsonian symptoms (eg, rigidity, bradykinesia, tremor) Trasmission:- Mosquitos (Culex spp.)- More common in summer/fall- Warm climate (southern United States, Latin America, Africa) Risk factors:- Older age- Malignancy/organ transplant
- Hepatitis B/C - Dramatically increases the risk of hepatocellular carcinoma- Ongoing infection with Hepatitis B or C virus leads to increased hepatocyte turnover and the generation of local inflammatory cytokines, which can lead in genetic mutations that lead to malignant transformation. HBV has several additional mechanisms that promote HCC:- Integration into the host genome – Nearly 90% of patients with chronic HBV who develop HCC have evidence of HBV DNA in the chromosome of tumor cells. HBV is a partially double-stranded DNA virus that is repaired by host cell machinery into a covalently closed circular DNA strand. - Production of oncogenic viral proteins – HBV produces a viral protein called HBx that is a transcriptional activator of several genes associated with cellular growth. It also interferes with the function of p53, an important tumor-suppressor protein.
- Naked viral genome infectivity Purified acids of most dsDNA (except poxvirus and HBV) and ⊕ strand ssRNA (≈mRNA) viruses are infectious. Naked nucleic acids of ⊝ strans ssRNA and dsRNA virses are not infectious. They require polymerases contained in the complete virion.
- Negative-stranded viruses Must transcribe ⊝ stand to ⊕. Virion brings its own RNA-dependent RNA polymerase. They include arenaviruses, bunyaviruses, paramyxoviruses, orthomyxoviruses, filoviruses, and rhabdoviruses.
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- Hepatitis viruses Signs and symptoms of all hepatitis viruses: - Episodes of fever- Jaundice- ↑ ALT and AST - Naked viruses (HAV, HEV) lack an envelope and are not destroyed by the gut. - HBV DNA polymerase has DNA- and RNA-dependent activities. Upon entry into nucleus, the polymerase completes the partial dsDNA. Host RNA polymerase transcribes mRNA from viral DNA to make viral proteins. The DNA polymerase then reverse transcribes viral RNA to DNA, which is the genome of the progeny virus. - HCV lacks 3'-5' exonuclease activity → no proofreading ability → variation in antigenic structures of HCV envelope proteins. Host antibody production lags behind production of new mutant strains of HCV.
- Hepatitis A virus Picornavirus (naked, ⊕ ssRNA) Transmission: Fecal-oral (shellfish, travelers, day care) Incubation: Short (weeks) Clinical course: Usually asymptomatic, acute No HCC risk. Liver biopsy: Hepatocyte swelling, monocyte infiltration. Councilman bodies. No carrier state.
- Hepatitis B virus Hepadnavirus (enveloped, dsDNA) Transmission: Parenteral (blood), sexual, perinatal - Binds to a bile salt transporter on hepatocytes. Uncoats in host cytoplasm. Single-stranded DNA portion is completed by cellular DNA polymerases. This dsDNA is transcribed by host RNA polymerase into ssRNA pregenome. Translated to proteins that compose the virus. RT converts it back into partially dsDNA progeny. Incubation: Long (months) Clinical course: Initially like serum sickness (fever, arthralgias, rash); may progress to carcinoma. Prognosis: Adults → mostly full resolution; neonates → worse prognosis. Liver biopsy: Granular eosinophilic "ground glass" appearance; cytotoxic T cells mediate damage.
- Hepatitis C virus Flavivirus (enveloped, ⊕ ssRNA) Transmission: Primarily blood (IVDU, post-transfusion) Incubation: Long Clinical course: May progress to cirrhosis or carcioma Prognosis: Majority develop stable, chronic hepatitis C Liver biopsy: Lymphoid aggregates with focal areas of macrovesicular steatosis.
- Hepatitis E virus Hepevirus (nonenveloped, ⊕ssRNA) Transmission: Fecal-oral, especially waterborne. Incubation: Short Clinical couse: - Prodromal: Fever, myalgia, nausea, vomiting- Icteric phase: Jaundice, dark urine, pale stools, prurtitus. Fulminant hepatitis in pregnant women. Prognosis: High mortality in pregnant women. Liver biopsy: Patchy necrosis.
- Perinatal hepatitis B infection Risk factors:- Maternal viral load- Maternal HBeAg positive Clinical findings:- Infants usually immune-tolerant (normal or mildly elevated liver enzymes, no symptoms)- High risk for chronic infection- High viral load & HBeAg positive Prevention:- Maternal antiviral therapy in some cases- Newborn hepatitis B vaccination & immunoglobulin within 12 hours- Routine immunization- Serology ~3 months after 3rd dose of vaccine
- Hantavirus Bunyavirus Reservoir: Deer mouseTransmission: Exposure to its droppings and urine Clinical presentation: Hantavirus pulmonary syndrome- Starts with fevers, headaches, severe mylagias, GI upset, dizziness, chills- Eventually pulmonary edema, cough, respiratory distress Treatment: Supportive
- Poliomyelitis Picornavirus. Unenveloped, ⊕ ssRNA. - Spread via fecal-oral transmission- Still endemic in Afghanistan, Nigeria, and Pakistan Clinical features:- Gastroenteritis, fever, nausea, sore throat, myalgia, and headaches for 1–3 daysWith CNS involvement:- Fever- Severe back, neck, and muscle pain- Asymmetric flaccid paralysis worsens over hours to days- Diminished deep tendon reflexes Diagnosis: PCR amplification of RNA from CSF Vaccines:- Sabin (livin) = Live attenuated- Salk (killed)
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