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University of Toronto St. George

LECTURE March 22, 2011 Antibodies neutralize pathogens Using HIV as example of a pathogenic infection Vaccinate in order to induce antibodies that neutralize infection, prevent infection from becoming established 1981 when HIV was first noticeable At then, not considered viral infection, but a bacterial infection This is not normally dangerous in immunocompetent people So unusual Kaposis sarcoma type of cancer seen rarely 1982 symptoms not restricted to homosexual groups Clear at that time that individuals suffering from this disease had lack of immune function, acquired because this was not inherited Looking at the history of the disease, AIDS was seen as infectious start of HIV epidemic AIDS description of symptoms Type 3 because there were already two other viruses known to infect human T cells 1986 causal agent of AIDS as a disease is the HIV virus Short time btw identifying new disease and epidemiological studies proving the disease was caused by infectious agent to discovering and characterizing the retrovirus called HIV all happened within 5 year span, at which point it was clear that AIDS was a new disease caused by a novel retrovirus called HIV Retroviruses Viruses do not contain all genetic material required for their lifecycle Retroviruses genetic information is RNA o RNA contains genetic information that allows for transmission of RNA retrovirus from one cell to next o First stage of process is reverse transcription of RNA back into DNA o Then DNA transcribed into RNA, then translated into protein to create new retroviral particles Extra stage: RNA reverse transcribed into DNA Unique opportunity to interfere with lifecyle of retroviruses Because no normal stage in higher organisms where RNA is required to be transcribed into DNA Potential place for drug targeting HIV is a retrovirus o Several families alpha, beta, gamma, delta, epsilon, spumaviruses, lentiviruses o HIV is part of Lentiviruses Lentiviruses named because they are slow-acting Each will infect target cell and long period of time, before symptoms are apparent Lentiviruses HIV-1 is most prevalent in humans SIVmac causes similar disease in monkeys, especially macacs EIAV not as closely related also like MVV not as closely related as the inner cluster o Interesting because there are related viruses that infect different species and in many causes, similar types of disease o Suggesting FIV, HIV2, SIV, HIV may be evolved from one another by crossing species THIS IS CALLED ZOONOSIS o Clear that HIV as a human virus has evolved from related viruses that were present in monkeys o Chimpanzees have simian immunodeficiency virus, related to HIV, around for longer than HIV o HIV-2 less virulent west Africa came from different species of monkey o Two independent examples of a disease of primates (non-human) that have crossed over into humans and ended up causing a disease o When viruses are established in non-human species, viruses may not be as pathogenic as in humans after crossing over EX. influenza carried in many birds, ex. ducks many strains replicate but cause virtually no symptoms Innocuous in natural host But when transferred into new host viruses like influenza cause severe symptoms ZOONOSIS has huge impact on ability to control infectious disease Smallpox arguably the most important success of the immune system because now eradicated o No animal host for smallpox o Because if can wipe out in humans, can wipe out globally o BUT it wouldnt matter if can vaccinate all against influenza, since it exists naturally in the world can return Zoonosis diseases infect non-humans and subsequently transfer disease to humans profound impact on ability to control disease HIV virus Genetic material is RNA One particle contains two RNA genomes, coated by capsid and matrix proteins that form the HIV core
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