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Our research is aimed at better understanding the interaction of HIV-1 with the host and what drives virus evolution during disease progression. We are interested in defining what HIV-1 induced immune responses or innate host factors can be associated with HIV-1 as a means towards developing HIV-1 vaccine or therapeutic agents.

We have studied the molecular interactions of the gp120 envelope with the CD4 receptor and an array of chemokine co-receptors (such as CCR5 and CXCR4) and the molecular events associated with co-receptor switching. Specific envelope alterations associated with co-receptor activity can influence the neutralization potential of the virus with either chemokines or specific monoclonal antibodies. Through studying longitudinal viral sequences from infected patients we have shown that escape from CTL epitopes can be associated with increasing viral loads and disease progression. We maintain that a complex network of immune and host factors govern viral replication and disease outcome.

More recently we have studied the effect of gp120 modifications on the interaction of HIV-1 with the DC-SIGN molecule expressed on the surface of dendritic cells, a molecule postulated to be invloved with viral transmission and early dissemination. Viruses of different envelope genotypes and phenotypes interact differently with DC-SIGN, which may help explain for selective transmission and propagation of certain viruses. We have more recently shown that the virus can interact with the DC-SIGN molecule in the presence of potent neutralizing antibodies and can infect CD4 lymphocytes, thereby providing a potential means of immune escape in the host. We have also identified a natural host factor in human milk that can bind to DC-SIGN and can prevent HIV-1 from binding and inhibit viral transfer to CD4 lymphocytes.