Pathogenic Viruses

1. Pathogenic Viruses • Name of virus • what family it belongs to • what disease it causes, organ system affected • DNA or RNA? • Route of transmission; reservoirs, vectors • Viral virulence factors (selected viruses) • Immunizations

2. A molecular biology lesson • RNA mutates more readily than DNA • Copying mistakes by the enzymes are not corrected • Not double stranded, so no mismatches noticed that can be fixed. • Many variants result • Less chance of lasting immunity • Harder to create vaccines

3. 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

4. HIV life cycle • Binding to host cell • Copying RNA into DNA by Rev Trans • Integration into host DNA • Transcription • Translation • Assembly and exit by budding www.aidsmeds.com/images/HIVLifeCycle1.gif

5. 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

6. 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

7. HPV • Papilloma virus • Cause of warts, in this case, genital warts • Virus tricks cell into preparing for cell division • Leads to greater susceptibility to cancer, particularly cervical cancer (and penile and anal cancer) • Especially those viral strains that aren’t good at causing actual warts • CDC researchers: estimated 20 million people in the US have human papillomavirus type16 (HPV-16) infections (50% of all cervical cancers)

8. Gardasil • New vaccine • Protects against HPV types 16, 18, 6, and 11 • These biotypes account for 70% of cases of cervical cancer and 90% of cases of genital warts. • Vaccine: a recombinant vaccine w/ capsid proteins • Estimate: 3,700 to die of cervical cancer in 2006 • Controversy: should it be mandatory? • Religious right, big Pharmaceutical lobby, etc.

9. 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.

10. 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

11. 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 • Vaccination now recommended • Because of bad result of early infection and great danger of liver damage, liver cancer. • Recombinant vaccine.

12. 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?

13. Orthomyxovirus • Influenza: a serious respiratory disease • Seasonal incidence • 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.

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

15. 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

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

17. 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 $

18. Eukaryotic Pathogens • Fungi • Protozoa • Not helminths (worms) in this lecture • Remember these are all eukaryotes, with organelles and many of the same cellular characteristics that humans have. • Makes drug treatment more difficult.

19. Fungi • Review basic fungal biology • Ascomycota, Zygomycota, Basidiomycota, based on sex • Unicellular or filamentous (molds), hyphae, mycelium • Often dimorphic • Yeast in body, mold in culture • Classification of fungal diseases (mycoses) • Superficial, cutaneous, subcutaneous • Systemic and opportunistic • Poisoning and allergies • Treatment • Azole drugs, amphotericin B, others

20. Common: cutaneous & opportunistic • Dermatophytes: various genera • Cause skin and nail diseases • Referred to as Tinea (worm) because of the ringlike appearance on scalp. • Cause ringworm, jock itch, athlete’s foot, etc. • Limited to outer layer of skin • Candida (candidiasis)- normal microbiota • Cause of vaginal infections, diaper rash, thrush • Capable of infecting any part of the body • Dangerous in cancer patients, HIV infections, etc.

21. Opportunistic infections • Aspergillus (aspergillosis) • Variety of species, very common in soil, plant materials • Serious infections in immunocompromised • Allergies to A. fumigatus • Poisoning from aflatoxin from A. flavus

22. Protozoans • Group responsible for human diseases are the animal-like protozoa. Old groupings: • Ciliates • Amoebae • Flagellates • Sporozoans (Apicomplexans) • Protozoa typically have life cycles • Simple, like vegetative and cyst found in amoebas • Complex, like sporozoans have

23. Rogue’s gallery-4 • Sporozoans • Plasmodium: the cause of malaria, several species • Involves mosquito, liver, red blood cells in a complex life cycle. • Features a synchronous bursting of RBCs with fever, delerium, followed by rest and recovery, then cycle • Number one cause of global mortality and morbidity Yearly: 300-500 million new cases; 1 million deaths. Intracellular plasmodia www.sirinet.net/ ~jgjohnso/plasmodium.html

24. Life cycle of Plasmodium www.sirinet.net/ ~jgjohnso/plasmodium.html