Distinct disulfide bonded region residues in gp41
The evolution of chemokine receptor (CKR) usage by HIV-1 in vivo is an important event as it is associated with accelerated disease progression. In ~ 50 % of infected individuals, it involves a switch from use of CCR5 as a fusion coreceptor (R5 viruses) to CXCR4 use alone (X4 viruses), or most commonly, in conjunction with CCR5 (R5X4 viruses). The complexity of R5X4 gp120-CKR interactions goes beyond the initial binding event as we have found that alternative CKRs evoke distinct conformational signals to the disulfide bonded region of gp41 in R5X4 Envs. This project will determine whether distinct disulfide bonded region residues in gp41 specifically respond to CCR5 versus CXCR4 in single R5X4 strains.
Funding Support:National Health and Medical Research Council (NHMRC)