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

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 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:

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