Investigation of the determinants of inter-subtype differences in HIV-1 Gag-drivenreplication capacity and their implications for HIV-1 transmissibility

HIV-1 subtypes have uneven prevalence and spread world-wide.  There is evidence to
suggest that there are differences in disease progression and transmissibility between
subtypes that may underlie the uneven prevalence and spread.  The biological mechanisms
that favour the success of one subtype over another are not fully understood, and
understanding these, especially the characteristics that favour high transmissibility, may help
in the design of strategies to curb the spread of HIV-1.  Mann’s research project aims to
contribute to the understanding of what makes one subtype more transmissible than
another.  The project will focus on the HIV Gag protein since its functionality has previously
been linked to subtype prevalence. Gag proteins of differing subtype and functionality will be
tested for their effect on the life-span of infected cells and the triggering of antiviral
responses.  The genetic determinants of differences in Gag functionality between subtypes
will also be further elucidated.