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Transcript
Remaining viruses • Hepatitis viruses – Hep A, B, and C. • Picornaviruses and common cold viruses • Influenza and the MMR group • HIV and sexually transmitted viruses • Mosquito-borne viruses of Arkansas • Sort of a mixture of groupings by type and groupings by disease. 1 Hepatitis 2 • Hepatitis is inflammation of the liver – Liver especially important in metabolism • Breakdown of drugs, toxins, waste products – Damage results in accumulation of bilirubin • Bilirubin is a stage in hemoglobin breakdown • Results in yellow color: jaundice – Hepatitis can be caused by several different viruses • Hepatitis A, B, and C viruses all cause liver damage, but are unrelated viruses. Hepatitis B 3 • A DNA virus: “Hepadnavirus” • Hepatitis B released from live cells, so accumulates in high numbers in body fluids. – Blood of infected person is rather infectious – Cuts, piercing, sex, childbirth, etc. – Large amounts of empty capsids ties up antibodies. • After exposure, long incubation, long disease – 10% have chronic infections – The younger the host, the likelier chronic infection Hep B continued • Chronic infection correlated with liver destruction – Liver tissue replaced by scar tissue; liver failure – Long term exposure to virus increases risk of liver cancer • Insertion of HBV DNA into chromosome may activate oncogenes • Vaccination now recommended – Because of bad result of early infection and great danger of liver damage, liver cancer. – Recombinant vaccine. 4 General model for viral carcinogenesis 5 Hepatitis A virus • A small RNA virus, “Picornavirus” – Transmitted by fecal-oral route – Incubation for 1 month, followed by fever, nausea, anorexia, jaundice • T cells attack infected liver cells – No chronic infections, patients recover. • Note comparisons to Hepatitis B: – RNA vs DNA – Shorter disease, few long term problems – Mode of spread completely different 6 Hepatitis C • Another RNA virus, different group: “Flavivirus” – Causes chronic infections >80% • Often mild with few symptoms until damage • Long period between infection and damage • Long term infections increase risk of cancer. – Transmission like Hep B: blood, sex, transplants Other viral Hepatitis: D, E, F, G, …more? 7 A molecular biology lesson 8 • DNA is copied faithfully – DNA polymerase has 3’ to 5’ exonuclease activity, a “backspace key” which deletes mistakes. – Other mechanisms exist to maintain fidelity. • RNA fidelity is not maintained – RNA polymerase does not backspace – Methods for monitoring RNA don’t exist • Many RNA viruses show high mutation rate – Many variants, immunity difficult. Picornaviruses • Small RNA viruses (“pico” = very small) – About 25 nm, near the size of a ribosome – Two kinds • Enteric viruses – includes Hepatitis A and polio • Only some cases of polio result in paralysis – Cause of many cases of “stomach flu” • Rhinoviruses: major cause of common cold – Rhino means nose 9 The Common cold 10 • Rhinoviruses have many serotypes – Variants, caused by easy mutation of RNA – Immune system can’t recognize all differences, but some protection with age. – Multiplies in narrow temperature range, nose/sinus cooler than body temperature • Other cold viruses – Coronavirus (best known cousin causes SARS) – Adenovirus (DNA virus), some serotypes cause GI infections Orthomyxovirus • Influenza: a serious respiratory disease – Virus has a segmented genome • 8 different RNA molecules – Spikes: Hemagglutinin and Neuraminidase • Major antigens recognized by immune system • Antigenic drift and shift – Drift: small mutations, making host susceptible • Requires new vaccine each year – Shift: major mixing of RNAs, whole new virus. 11 View of flu http://www.astrosurf.org/lombry/Bio/virus-influenza.jpg http://www-micro.msb.le.ac.uk/3035/3035pics/flusection.jpg 12 Nature of influenza • Attack on respiratory tract – Kills ciliated epithelial cells, allows bacterial infections. – Release of interferon from cells causes symptoms • H antigen (hemagglutinin) for attachment – That it agglutinates RBCs is an artifact • N antigen: neuraminidase – Cuts of the sugar on the glycoprotein receptor – Allows new virions to escape from cell without getting stuck 13 Role of H and N spikes and host cell polysaccharide 14 influenza • Changes in H and N (antigenic shift) – Mixing of viruses that infect birds, pigs, produce new strains able to jump to humans. – New antigenic type leaves population unprotected – Numerous epidemics throughout history • Flu of 1918-1919 killed 20 million – Asia watched very carefully: bird flu? • Flu vaccines made from deactivated viruses – Slow process (vaccine made in eggs), so every year correct strains are “guessed”. – Cell culture would be quicker but more $ 15 HIV: Human Immunodeficiency Virus 16 • Host range – Main types of cells infected: T helper cells and dendritic cells (including macrophages, microglia) • Have CD4 and CCR5 glycoproteins on surface • Infection process – RNA is copied into cDNA by reverse transcriptase – cDNA inserts into host chromosome – New RNA made – Protein precursor made, then processed; assembly occurs – Virions bud through cell membrane Disease process 17 • Chronic infection – T cells continually made, continually destroyed – Eventually, host loses • AIDS diagnosis: – Acquired Immuno Deficiency Syndrome • CD4 cell count below 200/µl; • opportunistic infections • Examples of opportunistic “infections” – Pneumocystis carinii pneumonia (PCP pneumonia) – Kaposi’s sarcoma; Tuberculosis; several others Prevention and Treatment • Prevention is easy – Practice monogamous sex, avoid shared needles – HIV cannot be spread by casual contact, skeeters • Drug treatment – Nucleoside analogs such as AZT – Protease inhibitors prevent processing of viral proteins Nifty animation at: http://www.hopkins-aids.edu/hiv_lifecycle/hivcycle_txt.html 18 Sexually transmitted viral diseases 19 • Herpes simplex II; Hepatitis B; HIV • Papilloma virus – Cause of warts, in this case, genital warts – Virus tricks cell into preparing for cell division • Protein E7 binds to pRB – Leads to greater susceptibility to cancer, particularly cervical cancer • Especially those viral strains that aren’t good at causing actual warts Paramyxoviruses • Family of RNA viruses related to the influenza family • Measles- Rubeola – Childhood disease, still a global cause of illness – Begins with respiratory infection, then fever and cold, then systemic with characteristic rash – Serious neurological complications in small percentage – Series of MMR vaccine; killed vaccine was ineffective • Mumps – Infection in URT and nodes, then viremia – Infection of glands, especially parotitis • Orchitis, meningitis, deafness are complications – Recent outbreaks in UK, Iowa. MMR vaccine 20 Paramyxoviruses-2 21 • Respiratory syncytial virus – Respiratory disease of children, no vaccine – Infants under 6 months may require hospitalization •Rubella – German Measles, a Togavirus •was once the major viral cause of birth defects. •Mild, kills few cells. •MMR vaccine important Arkansas Arboviruses • Not an official taxonomic group, but short for “arthropod-borne” – Includes Flaviviruses, Togaviruses, and others. – Zoonotic, spread from animals to people by arthropod vectors, especially mosquitoes. • Reservoirs may be birds, various mammals – Result in two main types of illnesses • Encephalitis, inflammation of the brain • Hemorrhagic fever: high fever with bleeding 22 Arkansas Arboviruses • Encephalitis: spread by skeeters – Eastern Equine encephalitis; • Togavirus; summer 2005, outbreak in NE US • Also infects, kills horses. Most dangerous. – St. Louis encephalitis, • Flaviviral diseases; Human disease. • Usually not serious. – West Nile virus • Flavivirus; imported to US, spread from NYC • Disease mostly in young and elderly 23