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"HIV Escape from Antiretrovirals and CTL Responses: Parallels and Differences" Dr. Simon Mallal (biography) English - 2004-07-21 - 40 minutes
(37 slides)
Summary : Dr. Mallal describes mechanisms by which HIV viruses escape from cytotoxic T lymphocytes (CTL) responses and anti-retroviral drugs. In the presentation, Dr. Mallal particularly focuses on HIV escape from CTL responses and hypothesizes on the selective pressure involved in generating these escape mutations.
It is well known that the molecular interaction of HIV epitopes with the major histocompatibility complex (MHC) molecule is delicate and depends on the amino acid sequences within the binding groove. Certain escape mutations aim to disrupt this interaction which allows the viral epitopes to circulate freely and thus remaining undetectable by CTLs.
Subsequent to HIV transmission from one host to the next, it is hypothesized that the virus begins to shed its escape mutations. Shortly after, the virus adapts to the human leukocyte antigen (HLA) profile of the host by generating alternative escape mutations. It is important to recognize that these escape mutation can, and most often do, come at a replicative cost.
Dr. Mallal presents the results of HIV reverse transcriptase sequencing in 2 cohort studies and their association with the HLA type, in turn supporting the hypothesis that escape mutations can in fact be HLA class 1 allele specific.
Learning objectives : After viewing this presentation the participants will be able to discuss:
The similarities and differences between HIV escape from CTL and anti-retroviral therapy.
The delicate interactions of HIV epitopes and MHC.
The implications of HLA alleles to viral escape.
The results which support the hypothesis that escape mutations are HLA class 1 specific.
Leslie AJ, Pfafferott KJ, Chetty P, Draenert R, Addo MM, Feeney M, Tang Y, Holmes EC, Allen T, Prado JG, Altfeld M, Brander C, Dixon C, Ramduth D, Jeena P, Thomas SA, St John A, Roach TA, Kupfer B, Luzzi G, Edwards A, Taylor G, Lyall H, Tudor-Williams G, Novelli V, Martinez-Picado J, Kiepiela P, Walker BD, Goulder PJ. HIV evolution: CTL escape mutation and reversion after transmission. Nat Med. 2004 Mar;10(3):282-9. Epub 2004 Feb 08.
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