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Transcript
Our selections for Spring 2006
• 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.
1
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
2
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
3
A molecular biology lesson
4
• 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.
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
5
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
6
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.
7
View of flu
http://www.astrosurf.org/lombry/Bio/virus-influenza.jpg
http://www-micro.msb.le.ac.uk/3035/3035pics/flusection.jpg
8
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
9
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 $
10
HIV: Human Immunodeficiency Virus
11
• 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
Disease process
12
• 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
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
13
Sexually transmitted viral diseases
14
• 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