Virology Quiz on Hepatitis and Arboviruses

Hepatitis Viruses

• Hepatitis viruses (A, B, C, D, E) primarily infect the liver.
• All have surface proteins reacting with hepatocyte cell surface receptors.
• They are non-cytotoxic; hepatocyte death results from cytotoxic T cells targeting viral antigens.
• Clinical manifestations often include fever, anorexia, nausea, vomiting, jaundice, dark urine, pale feces, and elevated transaminase levels.
• HAV is transmitted via fecal-oral route; HBV via blood, sexual contact, and during birth. HCV is transmitted via blood and sexual contact. HDV requires HBV coinfection; HEV transmitted via fecal-oral route.
• Hepatitis A and E typically have no carriers; B and C can develop chronic carriers.
• Relevant laboratory tests exist for diagnosing each, including IgM HAV, HBsAg, HBsAb, and IgM HBcAb for HBV. HCV tests and HDV tests (anti-delta Ag) are available.

Hepatitis A Virus (HAV)

• Single-stranded RNA virus transmitted by fecal-oral route.
• Humans are the only reservoir.
• HAV infections typically resolve spontaneously in less than 8 weeks.
• Incubation period 3-4 weeks. Most HAV infections are asymptomatic.
• No predisposition to later liver cancer.
• No antiviral therapy. Vaccination with inactivated HAV is available. Proper hygiene is crucial.

Hepatitis B Virus (HBV)

• DNA virus, containing DNA polymerase.
• Envelope contains surface antigen (HBsAg). HBeAg, another antigen, indicates viral transmissibility.
• Chronic HBV infection persists >6 months, increasing cirrhosis, liver failure, or hepatocellular carcinoma risk.
• ~80% of acute infections are asymptomatic in the U.S.
• ~22,000 new cases in the U.S. in 2015 alone.
• Treatment aims to reduce HBV DNA levels, and elevated alanine aminotransferase levels, for chronically infected patients. Seroconversion (inactive carrier phase) and achieving undetectable HBV DNA levels are treatment goals.
• Antiviral therapies (entecavir, tenofovir) available. Vaccination available using surface antigen (HBsAg)

Hepatitis C Virus (HCV)

• RNA virus.
• ~3.5 million people in the US have chronic HCV: >50% of acute infections become chronic.
• Treatment (DAA) aims to achieve sustained virological response (SVR): undetectable HCV RNA 12 weeks after treatment.
• SVR reduces liver-related health consequences (hepatocellular carcinoma, end-stage liver disease).
• Several direct-acting antiviral (DAA) agents available (sofosbuvir, ombitasvir, glecaprevir).
• No vaccine available.

Hepatitis D Virus (HDV)

• Satellite virus that requires HBV co-infection to replicate.
• Uses HBsAg as its envelope protein.
• Single-stranded RNA genome, negative sense, covalently closed.
• Encodes only one protein (delta antigen).
• Chronic HDV infection is generally more severe in those coinfected with HBV.
• Pegylated interferon alpha may reduce chronic hepatitis effects but not eliminate chronic carrier state. No antiviral therapy for HDV.

Hepatitis E Virus (HEV)

• Single-stranded RNA virus transmitted via the fecal-oral route.
• Common in developing countries. Similar to HAV but higher mortality rates in pregnant women (~30-100%).
• Fulminant hepatitis, liver failure, can occur. Most cases resolve without negative outcomes
• Treatment for immunocompetent patients relies on ribavirin; immunocompromised patients may require ribavirin. No vaccine available.

Arboviruses

• Diverse group of viruses transmitted by arthropods (e.g., ticks, mosquitoes).

• 600 different arboviruses.

• Named for the disease they cause or location of first isolation.
• Typically multiply in both vector (bloodsucking arthropod) and vertebrate host.
• Transmission via sufficient virus amount in the host's bloodstream.
• Only female arthropods transmit viruses.
• Incubation period= extrinsic incubation period= length of time for saliva to contain a sufficient amount of virus.
• Humans are dead end hosts. Low viremia and brief viremia occurs in humans, meaning there is low infection risk.

West Nile Virus

• Most common cause of arboviral encephalitis and meningitis in the U.S.
• Primarily transmitted by mosquitoes.
• Reservoir hosts are birds.
• Usually mild infections (~80% are asymptomatic).
• Some result in encephalitis and meningitis (~20% symptomatic).
• No antiviral treatment. No vaccine.

Zika Virus

• Transmitted by Aedes mosquitoes.
• Vertebrate host = humans and non-human primates.
• ~80% of infections are asymptomatic.
• Vertical transmission to fetuses can have profound fetal abnormalities (e.g., microcephaly) when infection occurs in the first trimester.
• No antiviral therapy; supportive therapy.
• No vaccine.
• Safe sex practices, use of mosquito repellant, and environmental measures to control mosquito populations.

Rabies Virus

• Enveloped virus with single-stranded RNA; bullet-shaped capsid, enclosed with lipoprotein.
• Negative sense RNA genome.
• Single serotype.
• Anigenicity from envelope glycoprotein spikes.
• Characterized by encephalitis.
• Reservoir: many mammals (bats, skunks, raccoons).
• Transmission: biting animal with rabies (virus enters saliva).
• Symptoms begin, rabies almost always fatal.
• No antiviral therapy; vaccination (and immunoglobulins) available for post-exposure prophylaxis.

Ebola Virus

• Enveloped virus; longest viruses.
• Single-stranded, non-segmented, negative sense RNA.
• Contains RNA-dependent RNA polymerase.
• Helical nucleocapsid.
• 5 strains (serotypes cross-react).
• Natural reservoir: unknown (likely fruit bats, rodents).
• Transmission: human-to-human via blood, body fluids, secretions.
• Secondary Transmission: from contact with infected blood, secretions.
• Needle/syringe re-use. May persist in survivor semen.
• High mortality rate (~90%).
• Symptoms include fever, headache, sore throat.
• Treatments include combination therapy of monoclonal antibodies (atolivimab/maftivimab/odesivimab).
• Vaccine available for Zaire ebolavirus. Proper handling of patient secretions important.

HIV (Human Immunodeficiency Virus)

• Retrovirus (RNA virus which reverse transcribes its RNA genome).
• Infects and kills helper CD4 T lymphocytes.
• Causes loss of cell-mediated immunity, increasing opportunistic infections.
• Other cells(displaying CD4 proteins on their surface) can also be infected.
• Treatments for chronic HIV includes inhibiting entry, reversing transcription (emtricitabine), inhibiting maturation, inhibiting genome integration into host genome (Raltegravir), and other treatments that inhibit protease enzymes.
• Prevention includes post-exposure prophylaxis (PEP) drugs to reduce risk of infection after potential exposure, Pre-exposure prophylaxis (PrEP) containing tenofovir or emtricitabine; circumscision can reduce infection risk.