Virology - 03 RNA Viruses

VIROLOGY BUNYAVIRIDAE RNA VIRUSES RNA VIRUSES GENERAL RULE • • • • • • • All are single stranded, Except: Reovirus All are enveloped, Except: Picornavirus, Calicivirus and Reovirus Generally helical, Except: Picornavirus, Reovirus, Retrovirus, Flavivirus, Togavirus All replicate in cytoplasm, Except: Orthomyxovirus, Retrovirus Latency is in oropharynx Largest is Paramyxovirus while Smallest is Picornavirus Arthropod borne • • • • • Arboviruses: infections spread by arthropod vectors Phlebovirus Rift Valley fever virus (RVF) Encephalitis and hepatitis Targets brain and liver BUNYAVIRUS • • LaCrosse encephalitis virus (LAC) o Aseptic encephalitis o Targets brain California encephalitis virus o Aseptic meningitis o Targets brain NAIROVIRUS • Congo-Crimean hemorrhagic fever virus (CCHF) o Hemorrhagic fever o Targets vascular endothelium and liver o High mortality HANTAAN, SEOUL, PUUMALA, AND DOBRA VIRUS • • Korean War Hemorrhagic fever with renal syndrome (HFRS) o Mostly Europe and Asia ▪ Exception: Seoul virus is worldwide SIN NOMBRE VIRUS (SNV) • • New world hantaviruses Hantavirus pulmonary syndrome (HPS) o Symptoms ▪ Hemorrhagic fever ▪ Develop tachycardia, hypoxia, and hypotension ▪ Thrombocytopenia, renal failure, shock, multiorgan system failure ▪ HPS: cough, symptoms, headache, GI, rapid progression to irreversible pulmonary edema o Transmission: Rodent urine and droppings CALICIVIRIDAE ARENAVIRIDAE • • • • • • "Old World" o Lymphocytic choriomeningitis (LCM) virus o Lassa viruses o Lassa-like viruses Mopeia "New World" o Tacaribe, Junin, Machupo, Amapari, Cupixi, Parana, Latino, Pichinde, Tamiami, Flexal, Guanarito etc. Latin term arena meaning sand due to its sandy and granular appearance under EM T shaped glycoprotein spikes with irregular shaped capsid with two segments Reservoir are rodents and bats Contact with excretions of rodents • • Norwalk and Norwalk-like viruses Sapoviruses o Acute gastroenteritis o Most common cause in ▪ Older children and adults in developed countries ▪ Schools, colleges, camps, cruise ships, nursing homes o Symptoms ▪ Severe nausea, vomiting, diarrhea, and lowgrade fever o Infection rates as high as 50% o Transmission ▪ Fecal-oral route ▪ Contaminated food and drinking water ▪ Swimming areas o Detection ▪ Viruses cannot grow in culture ▪ Electron microscopy or select reference labs perform serologic procedures ▪ EIAs for detection during outbreaks o CORONAVIRIDAE • • • Cause 15% of coldlike infections in adults Higher in children o Some pediatric diarrhea o Targets the GI tract o Transmitted person to person by direct contact, droplet, or airborne route ▪ Also found in urine and feces ▪ Also found in urine and feces Emerging infection o Severe acute respiratory syndrome coronavirus (SARS-CoV) o Symptoms ▪ Requires hospitalization and intensive care ▪ Can be rapidly spread with close patient contact • • ORTHOMYXOVIRIDAE • FILOVIRIDAE MARBURGVIRUS • • • Now Lake Victoria marburgvirus Symptoms of Lake Victoria marburgvirus o High fever 12 to 22 days o Maculopapular rash on trunk and extremities o Nausea, vomiting, and diarrhea o Diffuse hemorrhaging, shock, multiple organ system involvement ▪ High mortality Transmission o Contact with infected monkeys or infected patients • • • • Ebola - Sudan (EBO-S) Ebola - Zaire (EBO-Z) Ebola - Reston (EBO-R) Ebola virus Tai Forest strain (formerly Ivory Coast) Symptoms of Ebolavirus o Hemorrhagic fever ▪ Fever, chills, myalgia, and anorexia ▪ Sore throat, abdominal pain, diarrhea, vomiting, and bleeding from injection sites and the GI tract FLAVIVIRIDAE • • • Influenza A, B, C o Distinguish using Matrix (M) protein and nucleoprotein (NP) Mild to pandemic infections Variations: o Hemagglutinin (H) ▪ 16 different HAs o Neuraminidase (N) ▪ 9 different N Antigenic drift o Subtle changes in H or N antigens: point mutations Antigenic shift o Major changes in H or N antigens: new hemagglutinin or neuraminidase PARAMYXOVIRIDAE EBOLAVIRUS • • • • • Three cycles ▪ Sylvatic - Maintained in monkey populations by mosquitos ▪ Urban - Mosquito-infected person-mosquitoinfected person ▪ Intermediate - Mosquito-monkey-mosquitoperson-mosquito-monkey or person St. Louis Encephalitis (SLE) o Natural hosts: Birds o Transmission: Culex mosquitos West Nile Virus o Natural host: Birds o Transmission: Mosquitoes Japanese encephalitis virus (JE virus) o Ranges from influenza-like illness to encephalitis o Emerging pathogen Dengue fever virus o Breakbone fever o Four strains (1-4) o Symptoms ▪ Classic Dengue fever: mild disease ▪ Fever, headache, myalgia, bone pain, and sometimes a rash ▪ Self-limiting, nonfatal o Dengue hemorrhagic fever : severe disease ▪ Must be exposed to another strain of Dengue fever virus ▪ Classic Dengue fever with thrombocytopenia, hemorrhage, and shock Yellow Fever Virus o Natural host: Monkeys o Transmission: Aedes mosquitos - Africa, South America, Caribbean • • • • • • Morbillivirus Paramyxovirus o Parainfluenza 1 and 3 Pneumovirus Rubulavirus o Parainfluenza 2 and 4 Surface receptors o HN: hemagglutinin-neuraminidase ▪ Specificity of entry and attachment o F: fusion antigen ▪ Entry and spread Mumps Virus o Enveloped ssRNA virus o H and F antigens o Infectious parotitis o Swollen parotid glands ▪ May include swelling of testes, ovaries, and pancreas ▪ Can cause permanent sterility o Rare cases of meningitis reported o Vaccination has greatly reduced incidence of mumps (MMR) o Recent outbreak in lower Midwest, 2006 o Detection ▪ Swabs of the Stensen duct or of saliva ▪ Urine specimens ▪ Serology: fourfold rise in antibodies from paired sera MORBILLIVIRUS • • • • RETROVIRIDAE Also known as rubeola MMR vaccine Symptoms o Maculopapular rash with fever o On head and trunk o Whitish spots (Koplik’s spots) with red background Resolution of symptoms provides lifelong immunity • • • Require RNA-dependent DNA polymerase Oncovirinae o Human T-lymphotropic virus 1, 2, 5 (HTLV-1, HTLV-2, HTLV-5) o Cause leukemias, sarcomas, and lymphomas Lentivirinae o HIV-1 o HIV-2 PNEUMOVIRUS • • • • • RHABDOVIRIDAE Disease of infants; almost 100% by age 2 Incomplete immunity so children can continue to become infected Nosocomial infections in hospitals and clinics Can cause morbidity and mortality in elderly patients Transmission o Transmission by large particle droplets and fomites PICORNAVIRIDAE • Enteroviruses o Polioviruses 1-3 o Coxsackieviruses A1-23 o Coxsackieviruses B1-6 o Echoviruses 1-32 o Enteroviruses 68-72 • • • • • ENTEROVIRUSES • • • • Transmission o Via aerosol, fecal-oral, or fomites o Enter via alimentary canal Replicate in lymphoid tissue of pharynx and gut Spread to spinal cord, heart, or skin In polio, neurons are permanently destroyed POLIOVIRUS • • Majority of poliovirus thought to be eradicated Several vaccines available TOGAVIRIDAE • • • COXSACKIE VIRUS A • • • • Hand, foot, and mouth disease (HFMD) Primarily types A5, A10, and A16 Naked ssRNA viruses Transmission by fecal-oral route or fomites Myocarditis, pericarditis, possible involvement in cardiomyopathy RHINOVIRUSES • • Common cold o Nasal congestion, runny nose, sneezing, headache, sore throat, cough, sometimes bronchitis, rarely fever o Generally increased incidence during winter and spring Transmission o Aerosol droplets, fomites Alphavirus o Eastern equine encephalitis (EEE) o Western equine encephalitis (WEE) o Venezuelan equine encephalitis (VEE) Rubivirus o Rubella virus Arterivirus o No human cases SUPPLEMENTAL NOTES ARENAVIRIDAE • COXSACKIE VIRUS B • Lyssavirus Rabies o Endemic in most areas of the United States o Very diffuse animal pathogen that can infect humans o Raccoons, skunks, bats, foxes, cats, dogs, cattle, and coyotes Diagnosis - examine brain tissue Transmission o Bites or scratches from infected animals Symptoms o Pain in exposure site o Flulike symptoms and personality changes o Late stage ▪ CNS changes involving hallucinations, paralysis, excessive salivation, hydrophobia, bouts of terror, seizures, respiratory and cardiac problems; leads to coma and death • • Old World o Lymphocytic choriomeningitis (LCM) virus o Lassa viruses o Lassa-like viruses Mopeia New World o Tacaribe, Junin, Machupo, Amapari, Cupixi, Parana, Latino, Pichinde, Tamiami, Flexal, Guanarito etc. Transmission o Contact with excretions of rodents o Treatment o Ribavirin if started within 6 days of exposure NORWALK-LIKE VIRUSES CORONAVIRUS • • • EBOLA KOPLIK’S SPOTS • RETROVIRUSES • • HIV o Enveloped ssRNA virus ▪ Envelope contains 72 external spikes. ▪ Three groups of major antigens • Group-specific antigen/core (GAG) o p18, p24, p55 • Polymerase (POL) o p31, p51, p66 • Envelope (ENV) o gp41, gp120, gp160 (Entry) Diagram of HIV • • Transmission o Blood or exchange of body fluids (sexual contact) or congenital infection o Not transmitted by sweat, saliva, tears, urine, milk New cases in 2011 o Associated with: ▪ Heterosexual contact : 27% ▪ Men who have sex with men: 61% ▪ Intravenous (IV)-drug use: 9% ▪ Heterosexual contact and IV-drug use: 2% ▪ Transfusions of mother to infant :1% Common Opportunistic Infections and Cancers in patients with AIDS o Candidiasis of the respiratory tract o Coccidiomycosis o Cryptococcal meningitis o Cryptosporidiosis with persistent diarrhea o Cytomegalovirus infections of organs other than the liver, spleen, or lymph nodes o Histoplasmosis o Persistent herpes simplex virus infections o Kaposi sarcoma or lymphoma of the brain in patients <60 years o Oral hairy leukoplakia o Lymphoid interstitial pneumonia, pulmonary lymphoid hyperplasia, or both in children <13 years o Mycobacterium avium complex, Mycobacterium kansasii, or Pneumocystis jirovecii pneumonia o Recurrent pneumonia o Toxoplasmosis of the brain in infants >1 month o Wasting disease Disease course o Initial infection ▪ Transient febrile disease with lymphadenopathy, pharyngitis, or a diffuse rash ▪ High levels of circulating virus with absence of specific antibody ▪ Antibody develops in several weeks to months o Subclinical phase ▪ Antibody, circulating p24 antigen, low levels of circulating virus ▪ Virus continues to mutate to avoid immune cells and infects immune cells. Diagnosing HIV o Western blot ▪ Confirmatory test ▪ Positive: ≥2 bands p24, gp41, and gp120/160 ▪ Indeterminate: one band or other bands not listed above ▪ p66, p51, p31, p17, or others ▪ Negative: absence of any bands o EIAs and other tests are preliminary ▪ Cross-reactivity ▪ Retest positive EIA in duplicate ▪ Require confirmation Important Immunologic Markers for AIDS o Steady decline in number of CD4+ T cells o Depression of the CD4+ to CD8+ cell ratio to <0.9 (reference value, ≥1.5) o Functional impairment of monocytes and macrophages o decreased natural killer cell activity o anergy to recall antigens in skin tests • • • Reverse transcriptase inhibitors o Nucleoside analogs ▪ Azidothymidine, dideoxyinosine, d4T (stavudine), 3TC (lamivudine), and tenofovir o Non-nucleoside analogs ▪ Delavirdine, nevirapine, and efavirenz Viral protease inhibitors o Ritonavir, saquinavir, indinavir, and amprenavir Fusion inhibitors o T-20, enfuvirtide HAV TOGAVIRIDAE • • • • • EEE o Symptoms ▪ Influenza-like illness ▪ Develop encephalitis ▪ Fatal in 30% of cases ▪ Survivors usually have permanent CNS damage WEE o Symptoms ▪ Sometimes asymptomatic ▪ Fever, headache, nausea, mental status changes ▪ Develop encephalitis • 30% of infected children and infants suffer permanent CNS damage • Mortality, 3% VEE o Symptoms o Flulike illness o Develop encephalitis ▪ Primarily a small percentage of infected children and infants ▪ Not usually causing mortality Rubella virus or German measles o Mild febrile illness o Symptoms ▪ Erythematous, maculopapular rash starting on the face and moving down trunk and limbs ▪ No rash on palms and soles ▪ Transient arthritis may occur in children and adults ▪ Transplacental transmission to fetus • Can result in birth defects, fetal death, cataracts in fetus, and spontaneous abortion (congenital rubella syndrome) • • • • HBV • • • • • HEPATITIS VIRUSES • • Hepatitis Viruses o Hepatitis A (HAV) o Hepatitis B (HBV) o Hepatitis C (HCV) o Hepatitis D (HDV) o Hepatitis E (HEV) o Hepatitis G (HGV) o SEN virus o Transfusion transmitted virus (TTV) Clinical and Epidemiologic Differences of HAV, HBV, HDV, and Non-A/Non-B Hepatitis (NANBH) Enteric virus o Small icosahedral, naked ssRNA virus Transmission o Fecal-oral route ▪ Generally children between age 5 and 14 Symptoms o Acute self-limiting hepatitis ▪ Fever, chills, fatigue, malaise, aches, pains, and sometimes jaundice Diagnosis o Serology: HAV IgM antibody Vaccine is available • • Enveloped, partially dsDNA virus Chronic hepatitis; bloodborne pathogen Transmission o Blood and blood products o Needles o Sexual contact Symptoms o Infects liver cells, which undergo immune-mediated destruction o Fever, anorexia, hepatic tenderness, sometimes jaundice, elevated serum aminotransferase levels o Ninety percent resolve the infection without serious sequelae. o Ten percent become chronic carriers. ▪ High risk for cirrhosis, hepatic carcinoma Risk factors o IV-drug users o Men who have sex with men o Household contacts of those with HBV o Tattoos and piercings o Health care personnel o Neonatal infection Vaccine is available Serologic Markers for the Diagnosis of HBV Infection o HBsAg - hepatitis B surface antigen, the envelope protein consisting of three polypeptides o Anti-HBs - antibody to hepatitis B surface antigen o Anti-HBc - antibody to hepatitis B core antigen o HBeAg - antigen associated with the nucleocapsid, also found as soluble protein in serum o Anti-HBe - antibody to hepatitis Be antigen • Interpretation of HBV Serology Markers HEV • • • • HDV • • • • Delta hepatitis o Defective virus that requires HBV for replication o Requires HBsAg as its envelope Transmission o Blood and blood products o Sexual contact Infection o Coinfection: infection with HBV and HDV at the same time ▪ Greater likelihood of a more severe acute infection progressing to fulminant hepatitis o Superinfection: infection in chronic HBV carrier ▪ Chronic HDV, which increases the likelihood of cirrhosis Interpretation of HDV Infection Serologic Markers HCV • • • • • • • Bloodborne pathogen Transmission o Blood and blood products o Sexual contact Symptoms o Acute hepatitis less severe than HBV o Chronic in 50% of infected patients o Twenty percent of chronic carriers develop cirrhosis within 20 to 30 years. ▪ Cirrhosis increases the likelihood of liver cancer Risk factors o Blood exposure, usually transfusions o Sometimes sexual contact o IV-drug use Anti-HCV antibodies o Does not produce lifelong antibodies o Persistence indicates chronic infection Enzyme-linked immunosorbent assay (ELISA) screening test o c100 or 5-1-1, c33, c22 Recombinant immunoblot assay (RIBA) (Western blot) o No bands present: negative o One band (c100, 5-1-1 count as one): indeterminate o Two or more bands present: positive • Small, naked ssRNA virus Waterborne enteric agent o Fecal contamination of drinking water Similar to HAV Found in developing countries o Asia, Africa, and Central America o No U.S. sources Symptoms o Acute, self-limiting disease o Fever, malaise, nausea, vomiting, jaundice, and dark urine o Mortality is 1% to 3%, with greater mortality of 15% to 20% in pregnant women. OTHER HEPATITIS VIRUSES • • • HGV o Not common in United States SEN o Blood borne ▪ Circular DNA genome ▪ Possible link to hepatitis TTV o Post-transfusion hepatitis