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RNA Viruses

RNA Viruses. M.Tvorko. RNA Viruses. Diverse group of microbes Assigned to one of 12 families based on envelope, capsid, and nature of RNA genome. Enveloped Segmented Single-Stranded RNA Viruses. The Biology of Orthomyxoviruses: Influenza.

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RNA Viruses

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  1. RNA Viruses M.Tvorko

  2. RNA Viruses • Diverse group of microbes • Assigned to one of 12 families based on envelope, capsid, and nature of RNA genome

  3. Enveloped Segmented Single-Stranded RNA Viruses

  4. The Biology of Orthomyxoviruses: Influenza • 3 distinct influenza virus types: A, B, C; Type A causes most infections • Viral infection • Virus attaches to, and multiplies in, the cells of the respiratory tract • Segments of RNA genome enter the nucleus (transcribed/translated) • Finished viruses are assembled and budded off the cell with an envelope

  5. HA - hemagglutinin NA - neuraminidaze helical nucleocapsid (RNA minus NP protein Bilayer lipid membrane polymerase complex M1 protein ОRTHOMYXOVIRUSES types A, B, C : NP, M1 protein subtypes: HA or NA

  6. Key to influenza are glycoprotein spikes – • Hemagglutinin(H) – 15 different subtypes; most important virulence factor; binds to host cells • Neuraminidase (N) – 9 subtypes – hydrolyzes mucus and assists viral budding and release

  7. Hemagglutinin (HA)

  8. Influenza virus cycle

  9. Influenza A • In Birds • 16 HA A variants • 9 NA A variants • In Humans • 3 HA A variants • (H1, H2, and H3) • 2 NA A variants • (N1 and N2

  10. Both glycoproteins frequently undergo genetic changes decreasing the effectiveness of the host immune response • Constant mutation is called antigenic drift – gradually change their amino acid composition • Antigenic shift– one of the genes or RNA strands is substituted with a gene or strand from another influenza virus from a different animal host • Genome of virus consists of 10 genes encoded on 8 separate RNA strands

  11. Antigenic shift event

  12. Influenza B • Only undergo antigenic drift • Not known to undergo antigenic shift Influenza C • Known to cause only minor respiratory disease; probably not involved in epidemics

  13. Influenza A • Acute, highly contagious respiratory illness • Seasonal, pandemics; among top 10 causes of death in U.S. – most commonly among elderly and small children • Binds to ciliated cells of respiratory mucosa • Causes rapid shedding of cells, stripping the respiratory epithelium; severe inflammation • Fever, headache, myalgia, pharyngeal pain, shortness of breath, coughing • Weakened host defenses predispose patients to secondary bacterial infections, especially pneumonia

  14. Diagnosis, Treatment, Prevention • Rapid immunofluorescence tests to detect antigens in a pharyngeal specimen; serological testing to screen for antibody titer • Treatment: control symptoms; amantadine, rimantadine, zanamivir (Relenza), and oseltamivir (Tamiflu) • Flu virus has developed high rate of resistance to amantadine and rimantadine • Annual trivalent vaccine recommended

  15. Influenza Vaccines • Whole virus vaccine: inactivated virus vaccine grown in embryonated eggs; 70-90% effective in healthy persons <65 years of age, 30-70% in persons ≥65 years • Split virus vaccine: previously associated with fewer systemic reactions among the elderly and children <12 years • Subunit vaccine: composed of HA and NA • Live, attenutated influenza virus vaccines under development

  16. Enveloped Nonsegmented ssRNA Viruses

  17. Paramyxoviruses Paramyxoviruses (parainfluenza, mumps virus) Morbillivirus (measles virus) Pneumovirus (respiratory syncytia virus) • Respiratory transmission • Envelope has glycoprotein and F spikes that initiate cell-to-cell fusion • Fusion with neighboring cells – syncytium or multinucleate giant cells form

  18. PARAMYXOVIRUSES F glycoprotein SPIKES • HN/H/G glycoprotein helical nucleocapsid (RNA minus NP protein) polymerase complex M protein

  19. The effects of paramyxoviruses Insert figure 25.5 Effects of paramyxoviruses

  20. Parainfluenza • Widespread as influenza but more benign • Respiratory transmission • Seen mostly in children • Minor cold, bronchitis, bronchopneumonia, croup • No specific treatment available; supportive therapy

  21. Mumps • Epidemic parotitis; self-limited, associated with painful swelling of parotid salivary glands • Humans are the only reservoir • 40% of infections are subclinical; long-term immunity • 300 cases in U.S./year • Incubation 2-3 weeks fever, muscle pain and malaise, classic swelling of one or both cheeks • Usually uncomplicated invasion of other organs; in 20-30% of infected adult males, epididymis and testes become infected; sterility is rare • Symptomatic treatment • Live attenuated vaccine MMR

  22. Mumps

  23. Measles • Caused by Morbillivirus • Also known as red measles and rubeola • Different from German measles • Very contagious; transmitted by respiratory aerosols • Humans are the only reservoir • Less than 100 cases/yr in U.S.; frequent cause of death worldwide • Virus invades respiratory tract • Sore throat, dry cough, headache, conjunctivitis, lymphadenitis, fever, Koplik spots – oral lesions • Exanthem

  24. Signs and symptoms of measles

  25. Measles • Most serious complication is subacute sclerosing panencephalitis (SSPE), a progressive neurological degeneration of the cerebral cortex, white matter, and brain stem • 1 case in a million infections • Involves a defective virus spreading through the brain by cell fusion and destroys cells • Leads to coma and death in months or years • Attenuated viral vaccine MMR

  26. RESPIRATORY SYNCYTIAL (RS) VIRUS It is the single most serious cause of bronchiolitis and pneumonitis in infants. The particle is slightly smaller (80-120 nm) than other paramyxoviruses, and the nucleocapsid measures 11-15 nm. Although RS is one of the most labile of viruses. RS virus does not hemagglutinate.

  27. RSV Bronchiolitis- clinical features Symptoms for this disease are: sneezing runny nose sore throat low fever common cold symptoms just more severe.

  28. RSV is a viral disease. • Respiratory Syncytial Virus (RSV)is • a very serious virus often found in • children and infants under the age of three. • Adults are at very low risk of catching RSV.

  29. Rabies • Rhabdovirus family; genus Lyssavirus • Enveloped, bullet-shaped virions • Slow, progressive zoonotic disease • Primary reservoirs are wild mammals; it can be spread by both wild and domestic mammals by bites, scratches, and inhalation of droplets

  30. Structure of the rabies virus Insert figure 25.8 Structure of rabies virus

  31. Rabies Virus enters through bite, grows at trauma site for a week and multiplies, then enters nerve endings and advances toward the ganglia, spinal cord and brain Infection cycle completed when virus replicates in the salivary glands Clinical phases of rabies: Prodromal phase – fever, nausea, vomiting, headache, fatigue; some experience pain, burning, tingling sensations at site of wound Furious phase – agitation, disorientation, seizures, twitching, hydrophobia Dumb phase – paralyzed, disoriented, stuporous Progress to coma phase, resulting in death

  32. Pathologic pictures of rabies

  33. Often diagnosed at autopsy – intracellular inclusions (Negri bodies) in nervous tissue • Bite from wild or stray animals demands assessment of the animal, meticulous wound care, and specific treatment • Preventive therapy initiated if signs of rabies appear • Treatment – passive and active post exposure immunization • Infuse the wound with human rabies immune globulin (HRIG) and globulin; vaccination with human diploid cell vaccine (HDCV), an inactivated vaccine given in 6 doses with 2 boosters • Control – vaccination of domestic animals, elimination of strays, and strict quarantine practices • Live oral vaccine incorporated into bait for wild animals

  34. Arboviruses viruses that spread by arthropod vectors mosquitoes, ticks, flies, & gnats 400 viruses

  35. The Influence of the Vector Vectors and viruses tend to be clustered in the tropics and subtropics many temperate zones have periodic epidemics life cycles are closely tied to the ecology of the vectors peak incidence when the arthropod is actively feeding and reproducing Humans can serve as dead-end, accidental hosts or they can be a maintenance reservoir Controlling the vector controls the disease

  36. Characteristics of Arbovirus Infections Viral encephalitis brain, meninges, and spinal cord are involved convulsions, tremor, paralysis, loss of coordination, memory deficits, changes in speech and personality, coma survivors may experience permanent brain damage Treatment is supportive

  37. Togaviruses • Enveloped virion containing non-segmented, ssRNA (both + an – sense) ~11.7kb • Subspecies (i.e.: Rubella virus) causes Rubella or German Measles • Symptoms include low grade fever,sore throat, rash, and lymphoadenopathy • Viral RNA is complimented by the host cells machinery and the –’ve sense strand produced serves as a template for more +’ve sense strands

  38. Caused by Rubivirus, a Togavirus ssRNA with a loose envelope German measles Endemic disease Most cases reported are adolescents and young adults Transmitted through contact with respiratory secretions Rubella

  39. Rubella Two clinical forms: Postnatal rubella generally mild malaise, fever, sore throat, lymphadenopathy, rash lasting about 3 days Congenital rubella infection during 1st trimester most likely to induce miscarriage or multiple defects Diagnosis based on serological testing No specific treatment available Attenuated viral vaccine MMR

  40. Hemorrhagic Fevers Yellow fever eliminated in U.S. Two patterns of transmission: urban cycle humans and mosquitoes sylvan cycle forest monkeys and mosquitoes South America Acute fever, headache, muscle pain may progress to oral hemorrhage, nosebleed, vomiting, jaundice, and liver and kidney damage significant mortality rate

  41. Hemorrhagic Fevers Dengue fever flavivirus carried by Aedes mosquito usually mild infection dengue hemorrhagic shock syndrome, breakbone fever extreme muscle and joint pain can be fatal

  42. Spread by infected animals Hantavirus pulmonary syndrome (HPS) caused by a strain of hantavirus named “Sin Nombre” deer mouse is the host sheds the virus in saliva, urine, and feces Bunyavirus

  43. Model of Human Hepatitis C Virus Lipid Envelope Capsid Protein Nucleic Acid Envelope Glycoprotein E2 Envelope Glycoprotein E1

  44. Prevalence In Groups at Risk Recipients of clotting factors before 1987 75 - 90% Injection drug users 70 - 85% Long-term hemodialysis patients 10% Individuals with > 50 sexual partners 10% Recipients of blood prior to 1990 5% Infants born to infected mothers 5% Long-term sexual partners of HCV positive 1 - 5% Health workers after random needlesticks 1 - 2% HCV - Epidemiology

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