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DNA VIRUSES: ORGANISM Parvovirus (B19 virus) naked icosahedral ss linear DNA Papovavirus naked icosahedral ds circular, supercoiled DNA Adenovirus naked icosahedral ds linear DNA Poxvirus BIG complex envelope ds linear DNA Herpesvirus enveloped icosahedral ds linear DNA binds FGF receptor cell-mediated immune response multinucleated giant cells w/ intranuclear inclusion bodies alpha subgroup: HSV-1, HSV-2, VZV PATHOGENESIS / CLINICAL FEATURES erythema infectiousum (Fifth disease): affects children between 4-12 fever, “slapped face” rash transient aplastic anemia: virus stops production of RBC Human papilloma virus penetrates basal epithelial cells 1) common warts (1, 2, 4): most resolve in 1-2 years 2) genital warts (6,11): condylomata acuminata 3) cervical carcinoma (16, 18, 31, 33): intraepithelial neoplasia E6: p53 E7: Rb uncontrolled DNA synthesis BK Polyomavirus: mild infection in children JC Polyomavirus: progressive multifocal leukoencephalopathy (PML) in immunocompromised pts.: memory loss, poor speech, incoordination upper respiratory tract infections in children (4, 7): coughing, sneezing, rhinitis, sore throat, conjuctivitis can progress to lower respiratory tract pneumonia epidemic keratoconjunctivitis (Pink Eye), gastroenteritis, hemorrhagic cystitis only DNA virus to replicate in cytoplasm (own viral RNA polymerase) molluscum contagiosum: small, 1-2mm diameter, white bumps w/ central dimple respiratory aerosol or direct contact from skin lesions or fomites such as bedding HSV-1: >90% of adults in 40’s exposed saliva most are asymptomatic gingivostomatitis: painful swollen gums, mucous membranes w/ vesicles resolves in about 2 weeks; may have fever and other systemic symptoms herpes labialis (cold sores): milder, recurrent form vesicles on lips or nose keratoconjunctivitis: most common infectious cause of corneal blindness in US (stain of eye shows dendritic branching pattern of cornea) encephalitis: most common cause of viral encephalitis in US (temporal lobe): sudden onset fever and focal neurologic abnormalities treatable HSV-2: STD vesicles on vagina, cervix, vulva, penis painful with burning and itching fever and inguinal adenopathy neonatal herpes: transplacental transfer congenital defects/ encephalitis DIAGNOSIS / TREATMENT self-limited illness IV immunoglobulin during aplastic crisis koilocytosis: dark-stained nuclei surrounded by halo light nitrogen (freeze) surgery/ laser ablation podophylin or alpha-interferon: genital warts live, nonattenuated vaccines against some serotypes (4,7) used in military enteric-coated: no pathogenesis live, attenuated vaccinia vaccine eradication in 1977: no carrier state, easy recognition, single serotype Tzanck smear: Giemsa stain multinucleated giant cells Herpes acyclovir: encephalitis and systemic disease caused by HSV-1; also treatment for genital herpes acts on viral thymidine kinase, DNA polymerase shortens duration of lesions and reduces extent of shedding of virus HSV-1: latent in trigeminal ganglia HSV-2: latent in lumbar and sacral ganglia Herpes Virus 6 Herpes Virus 8 Varicella-Zoster Virus(VZV) infects respiratory tract w/ 2-week incubation viremia Cytomegalovirus (CMV) saliva, blood, semen, transplacental,peripartum roseola: high fever, truncal rash in children Kaposi’s sarcoma, multiple myeloma Varicella (chickenpox): very contagious; often during winter and spring fever, malaise, headache w/ rash (starts on face and trunk) red base w/ fluid-filled vesicle (papulesvesiclespustulescrusts) may progress to pneumonia and encephalitis in adults (rare though) Zoster (shingles): reactivation of latent VZV (stress or cell-mediated immunity) post-zoster neuralgia: burning, painful vesicles along course of sensory nerves (unilateral dermatome distribution) cytomegalic inclusion disease (transplacental or through mom’s milk): congenital abnormalities (mental retardation, microcephaly, deafness, seizures, jaundice, etc..) kidney histology w/ multinucleated cells w/ intranuclear inclusion bodies reactivate in immunocompromised: CMV retinitis, pnemonia, hepatitis Epstein-Barr Virus (EBV) infects B cells via C3 receptor mononucleosis: saliva (kissing) > 90% of adults have Ab (recovery in 2-3 wks) fever, very painful pharyngitis, lymphadenopathy, splenomegaly anorexia, lethargy prominent; hepatits and encephalitis in some patients early infection = milder disease Burkitt’s lymphoma: transforms B cells children in Africa (large mass on face) nasopharyngeal carcinoma (China and other parts of Asia) oral, hairy leukoplakia (seen in AIDS patients) Hepadnavirus (Hep B) enveloped icosahedral ds incomplete circular DNA (fragments) blood, sex, perinatally enveloped: more prone to environment RNA-dependent DNA synthesis: mRNA made used as template for genome DNA necrosis and inflammation of hepatocytes: cytotoxic Tcells risk of hepatocellular carcinoma long incubation (10-12 weeks) HBsAg: envelope protein indicating live virus and infection anti-HBcAg: acute IgM chronic IgG anti-HBsAg: for immunity HBeAg: indicator of transmissibility live, attenuated VZV vaccine VZ immunoglobulin as prophylaxis for immunocompromised patients acyclovir (acting through TK) Reye’s syndrome: encephalopathy and liver degeneration (assoc. w/ VZV and influenza B, esp. if with aspirin) VZV: latent in dorsal root ganglia ganciclovir: treat CMV retinitis and pneumonia for AIDS patients foscarnet: more side effects resistant to acyclovir (no TK) latent in WBC’s and kidney atypical CTL’s heterophile antibody: cross-reacts w/ and agglutinates sheep RBC’s IgM to viral capsid antigen (VCA): used in diagnostic test ”window period” of no HBsAg or HBsAb; only HBcAb active immunization: HBsAg protein infant at birth, 2, 4, 15 months 3 shots: teens and health workers RNA VIRUSES: ORTHOMYXOVIRUS Influenza virus segmented (-) ssRNA RNA-dependent RNA polymerase progeny RNA made in nucleus enveloped helical respiratory droplets PARAMYXOVIRUSES: Parainfluenza virus HA (+) NA (+) Respiratory Syncytial Virus (RSV) HA (-) NA (-) Measles HA (+) NA (-) Mumps HA (+) NA (+) TOGAVIRUSES: Rubella virus ss (+) RNA (+) HA enveloped icosahedral RHABDOVIRUSES: hemagglutinin interacts w/ sialic acid receptors on cell endocytosis uncoating acidification via M2 protein neuraminidase cleaves neuraminic acid on cell surface release of RNP EPIDEMICS: antigenic drift: viral replication mutations in proteins (every year) antigenic shift: rearrangement of segments major changes (every 10 years) 24-48 hr incubation: fever, myalgias, headache, cough; vomiting, diarrhea rare secondary bacterial pneumonia: S. aureus, S. pneumoniae one piece of ss (-) RNA only (+) RNA have infectious geome enveloped RNA-dependent RNA polymerase fusion protein: multinucleated giant cells Croup: acute laryngotracheobronchitis (larynx, trachea, bronchus) in children < 5 airway narrowing stridor (wheeze), barking cough, hoarseness fusion protein: produces multinucleated giant cells (syncytial cells) #1 cause of pneumonia in young children (esp. infants < 6 months of age) outbreaks every winter in hospitals and communities prior to rash, prodromal illness: after 2 week incubation fever, conjuctivitis (photophobia), rhinitis, coryza, hacking cough, malaise (feeling cruddy) Koplik’s spots: bright red lesions with blue-white centers on buccal mucosa rash: 2 days later maculopapular (bumpy) from face down to lower limbs complications: pneumonia, bacterial otitis media, encephalitis (subacute sclerosing panencephalitisfatal CNS disease), myocarditis infects upper respiratory infect disseminate to parotid glands (pain), ovaries, testes (orchitis sterility if bilateral), pancreas, and in some cases, meninges amantadine (inhibits uncoating): treat/ prevent only influenza A (not B) mainly elderly, unimmunized pts. also, derivative: rimantadine vaccine: killed influenza A and B Reye’s syndrome: encephalitis and liver disease in children w/ influenza or chicken pox given aspirin alpha virus: mosquito-borne fever, headache, encephalitis (EEE, WEE) rubivirus: rubellaincubate 2-3 wks mild febrile illness with rash (3d measles) congenital rubella syndrome: infect during 1st trimester teratogenic effects heart (patent ductus arteriosus), eyes (cataracts), brain (deafness, retardation) attaches to acetylcholine receptor on cell surface infects sensory neurons and posterior auricular lymphadenopathy adults (esp. women): polyarthritis IgM: recent infection IgG: immunity live, attenuated vaccine (MMR) Negri body (eosinophilic cytoplasmic limited (from IgA and IgG) immunity from previous infections ribavirin (effectiveness uncertain) live, attenuated vaccine part of MMR vaccine not give before 15 months of age since maternal Ab can neutralize virus live, attenuated vaccine part of MMR vaccine at 15 months of age Rabies virus ss (-) RNA lipoprotein envelope bullet-shaped capsid infects all mammals (raccoons, skunks, bats) moves by axonal transport to CNS rapid progression to death over 1-2 weeks REOVIRUSES: Rotavirus ds segmented RNA naked helical capsid PICORNAVIRUSES: Enteroviruses: infect enteric tract Poliovirus ”infectious RNA” limited to primates fecal-oral: oropharynx Coxsackieviruses fecal-oral route respiratory aerosol both can cause aseptic meningitis, mild paresis, and transient paralysis Echoviruses fecal-oral route Hepatitis A virus fecal-oral route rarely via blood viral gastroenteritis: profound dehydration, esp. in infants fever, abdominal pain, vomiting, diarrhea (no blood, no pus) > 50% of infant diarrhea requiring hospitalization in U.S. IV fluid replacement ss (+) RNA naked icosahedral nucleocapsid 3 serologic (antigenic) types (little cross rxn: need Ab against all 3 types) infects Peyer’s patch in small intestine and motor neurons in anterior horn 1) mild febrile illness headche, nausea/vomiting, sore throat resolves in most 2) aseptic meningitis 5-10 days later (fever, stiff neck, headache) 3) paralytic poliomyelitis (flaccid asymmetric paralysis w/ painful muscle spasms) possible respiratory paralysis in older patients death group A: herpangina vesicular pharyngitis w/ fever, vomiting, malaise hand-foot-and-mouth disease (fever and vesicular rash) group B: pleurodynia (epidemic myalgia) fever, pleuritic chest pain myocarditis/pericarditis chest pain, arrhythmias, cardiomyopathy, and heart failure (> 50% of viral causes) diabetes (possible role in juvenile diabetes in humans) one of the leading causes of aseptic (viral) meningitis enteric cytopathic human orphan also, “cold” rashes young children most frequently infected common outbreaks: fecally contaminated water or food (ie. raw oyster) nasuea/vomiting, fever, anorexia, jaundice dark urine, pale feces, AST/ALT most cases resolve spontaneously in 2-4 weeks w/ short incubation (3-4 wks) > 100 serologic types acid-labile Naked: stronger, less vulnerable! inactivated polio vaccine (Salk) w/ formalin-killed viruses: IV injected live attenuated poliovirus (Sabine): oral vaccine (preferred in US) induces secretory IgA to protect reversion virulence possible!! Rhinoviruses: prodrome: nonspecific symptoms fever, headache, sore throat, fatigue, nausea, anorexia, painfully sensitive nerves around healed wound site encephalitis: hyperactivity, agitation confusion, lethargy, seizures, madness hydrophobia (painful spasm of throat muscles upon swallowing), foaming inclusions inside infected neurons) vaccination of dogs, cats confine animals X 10 days signs? kill animal Negri body in brain? preexposure vaccine and human rabies immunoglobulin (RIG) no treatment or vaccine enteroviruses are most common cause of non-bacterial (aseptic) meningitis in U.S. Ig M antibody or 4X in IgG active immunity: inactivated HAV passive immunity: preformed Ig common cold: Coronaviruses, (common cold) best at 33 C ARBOVIRUSES: Togavirus ss (+) RNA enveloped icosahedral Flavivirus ss (+) RNA enveloped icosahedral Bunyavirus ss (-) segmented RNA enveloped helical Calciviruses ss (+) RNA naked icosahedral Deltavirus Arenaviruses ss circ. (-) RNA (2 seg) enveloped helical Filoviruses ss (-) RNA filaments highly pleomorphic Coronavirus ss (+) RNA enveloped club-shaped respiratory fingernose/eye incubation of 2-4 days sneezing, nasal discharge, sore throat, cough, headache transmitted by blood-sucking arthopods fever, encephalitis alpha virus (western/eastern equine encephalitis: WEE, EEE rural U.S.) EEE more sever than WEE sever headche, nausea/vomiting, seziures, coma rubivirus (rubella) PLEASE SEE ABOVE hepatitic C: milder form of hepatitis B Yellow fever (Panama canal workers): hepatitis, fever, backache Dengue fever (“breakbone fever”): muscle/joint aches, headache, hemorrhage, thrombocytopenia, septic shock endemic in Caribbean St. Louis encephalitis Japanese encephalitis (most common epidemic enc.) California encephalitis Rift Valley fever Hanta virus (Korean hemorrhagic fever): hemorrhagic fever with renal failure also, hantavirus pulmonary sydrome: high fevers, myalgias, cough, nausea/vomit Adenoviruses, Influenza C virus, Coxsackieviruses Hepatitis E: enterically-transmitted (fecally contaminated water); like Hep A monsoon flooding endemic to Asia, India, Africa, Central America Norwalk virus: outbreaks of gastroenteritis in schools, camps, cramped quarters Hepatitid D ss (-) RNA enveloped helical capsid co-infection w/ Hep B lymphocytic choriomeningitis virus: aseptic meningitis Lassa fever virus: severe, often fatal hemorrhagic fever w/ multi-organ involvement (lungs, heart, kidneys, and brain) Ebola and Marburg viruses: hemorrhagic fever (ie. Zaire outbreak) fever, headache, vomiting, diarrhea bleeding into GI intract shock and DIC high infectious: health care workers, family members (bodily fluids) upper respiratory tract infections common colds (20%) similar to Rhinovirus Hepatitis E: no prolonged carrier state Norwalk resolves spontaneously in 12-24 hours fulminant hepatitis, liver cirrhosis ribavirin to treat Lassa fever treat w/ alpha interferon live attenuated viral vaccine for Yellow Fever mosquito Aedes aegypti ribavirin for hantavirus pulmonary syndrome patients