Hepatitis viruses
Hepatitis A virus (HAV) |
Structure: icohahedral, naked, 27nm diameter. Picornaviridae. Enterovirus -72. withstands heating (boiling) and disinfectants. Spreads via oro-fecal route and uncooked shellfish (clams and oysters). (For the exam – only oro-fecal transmission). Incubation period 15-40 days. Abrupt symptoms: fever, nasuea, vomiting and jaundice due to necrosis of liver cells. Recovery complete in 8-12 weeks. Pediatric cases mild and undiagnosed. |
Picornaviridae |
Class IVa. Makes long single strand of mRNA |
Hepatitis B virus (HBV) |
Serum hepatitis, long term hepatitis. Hepadnaviridae (class VII). Viral coded DNA polymerase serves as reverse transcriptase. Danes particles in serum and viral surface antigen (most useful indicator). Danes particles, 42nm in diameter, found in patients serum. Incubation is 50-180 days. Blood bourne. Transdusion or contaminated needles. Oral and sexual transmission. Chronic carriers and IVDA are main source of infection. During later half of infection. Body fluids contain virus. Black fly has transmitted hep B (odd route, on an exam WRONG ANSWER). Symptoms: fever, rash, arthtitis) rare cases anicteric. Overall mortality ranges from 1-2%. 5-10% have HBsAG for life. 8-10% have high concentrations of Dane's particles. All carriers have anti-HBcAg and some have anti-HBeAg. Correlation w/ hepatocellular cecinoma |
Class VII replication |
Pregenomic RNA is in capsid w/ RNA polymerase that makes DNA. Once first DNA strand is made, the RNA is spliced and serves as a primer for the second strand. First strand is incomplete because of polymerase and the second because of the primer. |
HBV Surface antigen |
HBsAg. Non-soluble antigen. Most useful marker. Several subtypes have been identified. Detected in large quantities in infected serum, pleomorphic in shape under EM. |
HBeAg |
Indicator of serum infection. Virus can be transmitted. Part of core antigen. Cleavage product of viral core protein. |
HBcAg |
Observed in infected hepatocytes. Core antigen. Core protein has protein kinase activity. no free HBcAg in serum |
Dane's particle |
Whole HBV. |
HBV oncogenesis |
Tumor cells obtained from liver contain HBV-DNA. HBV carries no oncogenes, mechanism of oncogenesis unknown. Maybe insertional or transactivating mechanis. |
Anti-core antibody |
Surface antigen is the first to appear in large quantities. Anti-core antibody appears next in high quantitiy. Completely obsorbed by virus antigens, so not all antigens can be attacked (very high quantitiy). Eventually all HBsAg will be cleared, so anti-core antibody must also be detected because of this clearing. |
Chronic HBV |
Balance between surface antigen and antibody because body gives up. Windo period is early in infection. HBsAg falls for only a short period of time. Pg 30-7A. Anti-HBs and HBsAg. |
HBV control |
Screening of all blood for HBV (and HCV). Vaccines: inactivated (heptavax) and recombinant HBsAg (recombivax). |
HBV vaccine |
Only Anti-HBs antibodies. NO anti-HBc and NO antigens. Available for high risk individuals. |
HBV cleared infection |
Anti-HBs and anti-HBc. |
Retro v. hepadnavirididae (not imp) |
Reverese transcriptase activity. chronic infection of cells w/ destruction. Order of functional genes retro: gag-pol-env. Hepadna: C-P-S. Both can cause some cancers. |
Hepatitis C virus (HCV) |
Flaviviridae (class IVa) virus. Icosadedral w/ nucleocapsid. Sexual and IVDA transmission. Incubation 40 to 120 days. High liver enzymes used for prediction (ALT). 50% develop chronic liver disease and many develop cirrhosis and hepatocellular carcinoma |
Alanine amino transferase |
Liver enzyme that rises w/ liver damage |
HCV treatment |
No vaccine available. Prescreening of blood. PEGylated Inferferon Alpha for treatment. |
PEG |
Polyethylene glycol. Not very immunogenic. When attached to interferon alpha, it slowly detaches releasing interferon alpha slowing down interferon clearance. |
Hepatitis D virus (HDV) |
Enveloped agent. 35-40nm in diameter. Negative polarity ss negative circular RNA. Only one protein coded: delta antigen. Requires presence of HBV. Virus replication localized to the hepatocyte nuclei that do not contain HBcAg. Spreads through blood products and IVDA. Vertical transmission possible. Simultaneous infection of HBV and HDV results in mild infections. HDV infection subsequent to HBV infection results in rapid and severe hepatitis. |
HDV treatment |
Just treat HBV since it is a necessary precursor. Diagnosis by detection of anti-delta IgM and/or IgG. |
Hepatitis E virus (HEV) |
Caliciviridae. Small icosahedral naked virus. Transmitted to non-human primates through human feces (oro-fecal) and recovered from infected animals. Reservoir: pigs, rats, monkeys (all speculative). No vaccine |
Hepatitis F virus (HFV) |
Togaviridae. Oro-fecal. Icosahedral. No treatment |
Hepatitis G virus (HGV) |
ss positive RNA. |
Hepatitis TT virus |
Circoviridae (w/ negative polarity). Isolated in 1997. sexual, breast feeding transmission. No vaccines available. |
HHV 4 |
Human herpes 4. Epstein bar virus. Causes liver infection |
Yellow fever virus |
Causes liver infections |
Other viral infections (dntk) |
Cytomegalovirus, HHV 1, varicella virus, rubella (congenital rubella syndrome) |
Coxsackie B virus (dntk) |
Heart, muscle (pleurodynia) |
Cytomegalovirus (dntk) |
Kidney, glands |
Mumps (dntk) |
Glands |
HHV-1 (dntk) |
Liver, eye |
Eye infections (dntk) |
HHV 1, adenovirus, measles and rubella, enterovirus 70, coxsackie A24 virus |
Betaherpesvirinae*** |
Long viral replication cycle (48hrs). Infected cells are swollen (cytomegaly), not lysed. Latency in glands, kidney and liver. |
Alphaherpesvirinae |
Short cycle. |
Gammaherpesvirinae |
|
HHV 5 |
Cytomegalovirus. Mostly subclincial. Breast milk, saliva, urine, semen, genital secretions. Shed virus for long time. Giant cells w/ cowdry type A inclusion bodies. 50% of babies ofund infected when mothers had primary infection during pregnancy. Latent infection life long. Virus shed in saliva and urine for months to years after primary infection (active form). |
Congenital CMV |
20% symptomatic. Jaundice, microencephly, hepatospleenomegaly and lethargy. Asymptomatic infants develop viruria within 1 week after birth |
Perinatal CMV |
Vast majority asymptomatic. Pneumonitis may be seen occasionally during first 3 months |
Immunocompromised CMV |
Leukemia and lymphoma patients at high risk. CMV retinitis, colitis and pneumonia in AIDS patients. |
Adenovirus |
Resistent to ether. Icosahedreal. 80nm. VA-RNA early RNA that blocks interferon induction. Diagnosis: nuclear inclusion bodies in infected cells. Isolated from tonsils, nasopharynx and intestinal tract of healthy individuals. About 45% of infections result in disease. Oro-fecal and respiratory tract spread during childhood. ***Common group specific CF antigen associated with the HEXON |
CMV diagnosis |
Virus isolation from saliva and urine. EM observation of virus in urine. RIA and ELISA |
Gancylclovir |
CMV |
Acyclovir |
CMV |
Refampin |
Adenovirus. |
Serology test |
****4 fold increase in titer. Paired test. |
Hemorrhagic Fevers
Hemorrhagic fevers |
Four families (Flavi, Arena, Bunya and filoviridae). No vaccines |
Tetracycline |
Increasingly used to treat all hemorrhagic fever |
Diagnosis |
Serology and virus isolation or genome amplification by PCR |
Flaviviruses |
Class IVa. Arbovirus (except HCV). All flaviviruses serologically related cross reacting antibodies. Transmitted by insects. Infect macrophages. Cell damage by cell mediators. Tissue destruction by T-cells. Shock syndrome |
Shock syndrome |
virus-antibody complex enters monocytes via Fic rec. antibody enhances infection. Increased production of cytokines. Severe illness, hemorrhages, shock |
Dengue fever |
Flaviviridae. Fever, rash, hemorrhagic shock syndrome. Mosquitoes, reservoir unknown. India, SE Asia, Pacific, South America, and the Caribbean, no vaccine available, vector control. Second infection worse than first. Carribean strain is mild; asia strain is bad. |
Arenaviridae |
Class V. Small positive sense segment to make enzymes. Host ribosomes trapped in viral particle w/ no known function. Looks like sand. Reservoir in rats. Spreads through rat feces and urine |
Lassa fever |
Arenavirus. Siera Leone. African bush rat. West Africa. 10/21 doctors and nurses died. Diagnosis by CSF and blood. Fever, diarrhea, hemorrhages, hemoconcentration and collapse. Treatment is give saline. Human-human transmission is unknown. 10-50% mortality |
Bolivian hemorrhagic fever |
Arenavirus. Machupovirus. Bush mouse. NE bolivia. 15% mortality. Fever, myalgia, hemorrhage, shock and neurologic illness. 15% mortality. DDT given to mosqitoes. Mosqitoes eaten by something that is eaten by cats. Cats die, so rats increase. |
Argentinean hemorrhagic fever |
Arenavirus. Juninvirus. Fever, myalgia, hemorrhages, collapse. Callomys spp. Of mice. 10% mortality |
Venezuelan hemorrhagic fever |
Arenavirus. Guanaritovirus. Fever, headache, sore throat, pharyngitis, loss of apetite, nausea, comiting, seizures and nose and gum bleeding. 30-40% mortality. No vaccine; rat control. Cane rats and cotton rats |
Bunyaviridae |
Class V. reservoir in rats, mice, and ticks. Plasma and RBCs leak through vascular epithelium |
Korean hemorrhagic fever |
Bunyaviridae. Hantaan virus. SW United States. Hemorrhagic fever w/ renal syndrome. No vaccine. Rodent control. Far east, Scandinavia, E. Europe. |
Congo-crimean hemorrhagic fever |
Bunyaviridae. Niarovirus. Asia, africa. Rodent reservoir, transmitted by ticks. Current epidemic. No vaccine. Rodent and tick control |
Filoviridae |
Class V. In areas w/ apes and chimpanzes. So far confined to Africa. |
Marburg hemorrhagic fever |
Filovirus. Marburgvirus. Identified in Germany after Ugandan Monkeys brought in. 20% mortality. Fever, rash, hemorrhage, probably DIC. No known reservoir |
Ebola disease |
Filovirus. Ebolavirus. Sudan febrile illness, vascular collapse, internal bleeding, death, Sudan and Zaire, no known reservoir or vector. 1976 first case. 90% mortality. Glycoprotein peplomers cause destruction of endothelium of blood vessels resulting massive hemorrhages. 4 recognized strains: Zaire, Sudan, Reston (nonpathogenic), Cote d'Ivoire. |