1. Our selections for Fall 2005 Herpes Virus family –HSV 1 & 2; VZV; EBV, and CMV Hepatitis viruses –Hep A, B, and C. Mosquito-borne viruses of Arkansas Picornaviruses and common cold viruses Influenza HIV and sexually transmitted viruses Sort of a mixture of groupings by type and groupings by disease.

2. 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

3. 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

4. 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.

5. 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

6. 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

7. 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.

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

9. Nature of influenza Attack on respiratory tract –Kills ciliated epithelial cells, allows bacterial infections. –Release of interferon 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

10. 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 $

11. 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

12. 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

13. 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