The Role of APOBEC Targeting of the HIV Genome in Human Adaptive Immunity
28 الي 30 بهمن 1389، شيراز - ايران
Presentation Type: Speech
Apobec3G (A3G) and Apobec3F (A3F) are 2 members of an 11-member APOBEC family of enzymes which are expressed in lymphocytes, dendritic cells and monocytes and restrict HIV propagation in cell culture assays. It has been shown that A3G/A3F packaged into the virion rather than the A3G/A3F in the newly infected cell, carry out the HIV-restricting activity. The mechanism is not understood but it may be the sequestration of the bulk of cytoplasmic A3G/A3F in high molecular mass complexes (HMM) up to 1 mega-dalton in size, rendering them ineffective. Thus encapsidation is critical for A3G/A3F function. The function of the virion infectivity factor (Vif) is to prevent encapsidation of A3G/A3F by binding and marking them for degredation through the ubiquitin-dependent proteosome. Much recent work has resulted in our understanding of A3G/A3F as agents of innate immunity; however, it has not been investigated whether these also mediate an effect on adaptive immunity. It is possible that low-level A3G/A3F mutations which do not render the genetic code completely non-sense, may in some cases tilt the balance in favor of the virus. The consequences are important since A3G/A3F are held in check by Vif and HMMs and hence, their activity on the viral genome results in non-deactivating low-level mutation patterns in the majority of instances. It has been suggested that suboptimal mutation of viral DNA by A3G/A3F could lead to drug resistance or immune-escape of cytotoxic T cell (CTL) response variants. The flip side, that is whether A3G/A3F mutations of the HIV genome can lead to the generation of more immunogenic CTL epitopes, has not been considered. Here we present our investigations on how mutation of specific CTL epitopes of HIV by APOBECs can affect the cytotoxic T cell response to the virus.