Remaining viruses

1. 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.

2. Hepatitis • 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.

3. Hepatitis B • 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

4. 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.

5. General model for viral carcinogenesis

6. 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

7. 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?

8. A molecular biology lesson • 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.

9. 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

10. The Common cold • 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

11. 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.

12. View of flu http://www.astrosurf.org/lombry/Bio/virus-influenza.jpg http://www-micro.msb.le.ac.uk/3035/3035pics/flusection.jpg

13. 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

14. Role of H and N spikes and host cell polysaccharide

15. 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 $

16. HIV: Human Immunodeficiency Virus • 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

17. Disease process • 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

18. 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

19. Sexually transmitted viral diseases • 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

20. 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

21. Paramyxoviruses-2 • 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

22. 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

23. 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