Fig Specialized Transduction. Vaccinia Virus. What is a Virus? Outline of Lecture. Result = horizontal gene transfer Fig. 13.

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1 Viruses and Prions Outline of Lecture Viral basics and interesting facts Three interactions with host Influenza, herpes, genital warts HIV-AIDS Prions Discussion question--can viruses be beneficial? Questions welcome anytime! What is a Virus? 1. Viruses are obligate intracellular, molecular parasites 2. Very small and infectious 3. The virus genome--either of DNA or RNA 4. Viral genome directs the production of new virus particles Figure 13.3 Fig Fig A. Naked virus B. Enveloped virus. Many animal viruses. Spike proteins are also often attachment proteins that attach to specific sites host cell. Envelope derived from host plasma membrane Specialized Transduction Edward Jenner Vaccinia Virus First vaccine Result = horizontal gene transfer Fig

2 Different Interactions with Host Influenza (pp ) Fig (modified) > Highly mutable virus - changes antigens very quickly > Many animal reservoirs 1. Host cell bursts 2. Host cell survives, genome modified, Viral leakage 3. Host cell survives genome modified, new host characteristics Influenza Herpes HPV Influenza (flu) virus is a ss, RNA, enveloped virus (Fig ) that infects cells of the respiratory tract. The Neuraminidase (N) protein on the viral surface hydrolyzes the host mucous coating allowing the Hemagglutinin (H) to bind to protein receptors on mucosal cells The virus is taken up and H fuses with the membrane causing the viral RNA to be released into the cytoplasm Continually evolving New strain(s) every year Variants (via mutations and genetic rearrangement) of last year s virus H changes slightly H becomes new antigen not recognized by last year s antibodies New shot every year Influenza--Humanity evolution arms race Major rearrangements (antigenic shift) "antigenic drift" = year to year minor variations (mutations) in the viral membrane proteins "antigenic shift" = major changes in these proteins Major change was cause of deadly pandemics (e.g and 1957) Possible genetic rearrangement among duck, swine and human flu viruses (probably in pigs) -more than one strain of flu -infect a single cell at the same time Thus during assembly of the viruses -eight different segments of the viral genome -mixed and matched into new viruses -major new antigenic presentation See Fig > Influenza caused worst world pandemic in , killing over 20 million people (about 80% of the American casualties during WWI)

3 > Viruses are inhaled or ingested. Spread via sneezing and coughing!results in fever, chills, headache, aches!most of the symptoms are caused by virus lysis (bursting) cells of the respiratory tract!leads to secondary infections by bacteria and other viruses Herpes See Fig > Death occurs due to secondary infections > 10,000-40,000 deaths due to flu every year Genital Warts probably most common sexually transmitted disease. (pp ) Cause = human papillomavirus (HPV) naked viruses resistant to drying At least 50 different HPVs cause tumors (malignant and/or benign) Warts are benign tumors HPV of genital warts are related to HPVs that cause cancer HPV-16 --> cervical cancer in the USA = 7% of all cancers in females (5000 deaths annually). PAP test detects early. HPVs are ds DNA viruses incorporated into host chromosome or becomes plasmid cause infected cell to multiply more rapidly than normal --> tumor Cancer causing Papillomaviruses code for proteins that inhibit anti-oncogenes Worrisome pandemic of genital warts --> Cancer causing forms just as easily transmitted as wart-causing Both often both found in women with cervical cancer HPV Prevention/Treatment No sex with people with warts (duh) Condoms Avoid sex with people with multiple partners PAP tests regularly Wart removal DOES NOT cure cancer causing infection

4 pp HIV!First described in !Epidemiologists predicted a blood-borne virus! Gallo linked a retrovirus to immunodeficiency syndrome, AIDS More than 33 million people infected worldwide 16 million have died The Toll of AIDS Fourth leading cause of death in the world. Fig AIDS pandemic as of 2001 Fig Percentage of AIDS cases in women in the USA. Human Immunodeficieny Viruses Retrovirus - ss RNA infect mononuclear phagocytes HIV targets cells with CD4 receptors See Fig Life Cycle of HIV Fig The Three Phases of HIV Disease HIV infection--most infected cells show no lysis (bursting) no latency (integrated genome, no virus produced) accumulating and releasing viral products (integrated genome) Fig Blood levels of HIV virus--red circulating HIV RNA--green CD4 cells--blue

5 Epidemiology of HIV Transmitted via: sexual intercourse blood and blood products mother to infant Vaccine? No vaccine for HIV (yet) HIV constantly changing its proteins (evolution) Sloppy reverse transcriptase-->high mutation rates-->high evolution rate Treatment Problems with HAART Antiviral cocktails HAART = highly active anti-retroviral therapy = Mixture of inhibitors: -reverse transcriptase (e.g. AZT) PLUS -protease Combined therapy especially effective. Why? Drug toxicity and inconvenience. Expense. Viral Drug Resistance. Residual Virus Replication. HIV continues to replicate because drugs do not penetrate all tissues/compartments. Long-Lived Reservoirs of Virus Infection. Prions - infectious protein particles - cause diseases in animals and humans - Prions--the only infectious agents that do NOT contain any nucleic acids - Cause brain diseases in -sheep (scrapie) -cows (mad cow disease, BSE) -humans (Kuru and Creutzfeld-Jakob disease) -elk/deer (Chronic Wasting Disease) - Result of prion diseases = holes in brain tissue, sponge-like appearance (thus "spongiform encephalitis") - All caused by exposure to brains - Kuru was figured out by Gajdusek - spread via burial ceremonies - people smeared brains of dead relatives on their bodies (see Table 14.12).

6 Mad Cow Disease BSE -bovine spongiform encephalopathy (BSE) -British added ground up sheep & cows to cattle feed -cattle then ground up and fed to humans (burgers!) -Prions are not destroyed by cooking latent period up to 15 years? long time before full impact on people in Britain is known detected recently (2003) in a cow in the USA -incidence of Creutzfeld-Jakob disease in humans recently increased in Britain Clin Lab Med Dec; 22(4): Variant Creutzfeldt-Jakob disease and bovine spongiform encephalopathy. Belay, E.D., and L.B. Schonberger. Abstract: Strong epidemiologic and laboratory evidence indicate that a novel, variant form of Creutzfeldt-Jakob disease (vcjd) first reported in the United Kingdom in 1996 is causally linked with bovine spongiform encephalopathy (BSE). BSE was first identified in the early 1980s in the United Kingdom, and has since spread to other European countries and recently to Japan and Israel. Although the United Kingdom BSE epizootic is on the decline, widespread exposure of humans to infected cattle products may have already occurred, raising concerns about the ultimate magnitude of the vcjd outbreak which, as of October 2002, has already affected 138 patients worldwide, including 128 patients in the United Kingdom. Emerging Infectious Diseases Vol. 10, Number 6, June 2004 Chronic Wasting Disease and Potential Transmission to Humans E.D. Belay, R. A. Maddox, E.S. Williams, M. W. Miller, P. Gambetti, and L.B. Schonberger Chronic wasting disease (CWD) of deer and elk is endemic in a tri-corner area of Colorado, Wyoming, and Nebraska, and new foci of CWD have been detected in other parts of the United States. Although detection in some areas may be related to increased surveillance, introduction of CWD due to translocation or natural migration of animals may account for some new foci of infection. Increasing spread of CWD has raised concerns about the potential for increasing human exposure to the CWD agent. The foodborne transmission of bovine spongiform encephalopathy to humans indicates that the species barrier may not completely protect humans from animal prion diseases. Conversion of human prion protein by CWD-associated prions has been demonstrated in an in-vitro cell-free experiment, but limited investigations have not identified strong evidence for CWD transmission to humans. More epidemiologic and laboratory studies are needed to monitor the possibility of such transmissions. Figure. Chronic wasting disease among free-ranging deer and elk by county, United States. How do prions cause disease and replicate without nucleic acids? First idea--inducers or repressors of gene expression The latest theory--recruit proteins similar to themselves in the membranes of brain cells From: E.D. Belay, R. A. Maddox, E.S. Williams, M. W. Miller, P. Gambetti, and L.B. Schonberger Chronic Wasting Disease and Potential Transmission to Humans Emerging Infectious Diseases 10(6), June 2004

7 Proposed mechanism for prion replication - prions line up next to similar proteins that line brain cells - cause a shift in their tertiary structure to the prion form - causes the outer lining of brain cells to become rigid and cavity forming. Beneficial Microbes Cyanobacteria--atmospheric O 2 Rhizobium--N fixation, soil fertility Rumen flora--digest cellulose in horses E.coli and others--protective intestinal flora Mitochondrion--ATP Etc. Fig Discussion Question Are viruses always harmful? Are they ever beneficial? Brainstorm ideas Small groups 3 to 5 people per group 5 minutes to meet Compile group s ideas--spokesperson QUESTION: in what ways could viruses be beneficial? Ideas Protection against disease Vaccinia Ecological Australian rabbits and viral eco-control Host modification Turn on anti-oncogenes Manipulate gene expression As vectors Transfer useful genes to other hosts Gene therapy Target viruses to kill tumor cells

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