1Pathogenic 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

2A 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

3HIV: 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

HIV life cycle4

www.aidsmeds.com/images/HIVLifeCycle1.gif

1. Binding to host cell2. Copying RNA into

DNA by Rev Trans3. Integration into host

DNA4. Transcription5. Translation6. Assembly and exit

by budding

5Disease 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

6Prevention 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

7HPV

• 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)

8Gardasil

• 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.

9Hepatitis

• 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.

10Hepatitis 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

11Hep 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.

12Hepatitis 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?

13Orthomyxovirus

• 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.

14View of flu

http://www.astrosurf.org/lombry/Bio/virus-influenza.jpg

http://www-micro.msb.le.ac.uk/3035/3035pics/flusection.jpg

15Nature 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

16Role of H and N spikes and host cell

polysaccharide

17influenza

• 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 $

18Eukaryotic 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.

19Fungi• 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

20Common: 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.

21Opportunistic 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

22Protozoans

• 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

23Rogue’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

Intracellular plasmodia

www.sirinet.net/ ~jgjohnso/plasmodium.html

Yearly: 300-500 million new cases;

1 million deaths.

24

Life cycle of Plasmodium

www.sirinet.net/ ~jgjohnso/plasmodium.html