Simian Immunodeficiency Virus Pathogenesis and Immunity
Extensive genetic diversity is a characteristic of HIV and its macaque homolog simian immunodeficiency virus (SIV). In each infected individual, the virus and the immune system engage in an unrelenting game of hide and seek. In some cases, the immune system pressures the virus to mutate in ways that hinder its ability to replicate. In other individuals, the immune system is weak and does little to impact the viral replication. The quality of an individual’s immune response is dictated, in part, by his or her genetics. One reason why HIV and SIV are so frustrating to study is because these viruses behave differently in each genetically distinct host.
1) SIV Pathogenesis in Macaques with Identical Immune Genetics
There are only a few isolated reports of HIV infection in genetically identical twins infected with the same HIV strain. Is HIV pathogenesis and immunity reproducible in these individuals? Currently available data is inconclusive. Therefore, we are infecting macaques with identical immunogenetics with the same strain of SIV to determine which elements of pathogenesis are controlled by host genetics. We now know that the virus mutates in the same regions in MHC-identical macaques (such as CY0111 and CY0113, shown below), but we do not yet know whether this correlates with similar rates of disease progression to AIDS. Ongoing projects in the lab are studying pathogenesis and T cell immunity in genetically defined macaques.
2) Mucosal immunity and SIV pathogenesis
Earlier this year, members of the lab asked to begin studying T cell homing and immune responses in mucosal tissues. There is a massive loss of CD4+ T cells located in the gut mucosa in the first weeks of HIV and SIV infections. Are T cell responses measured in the blood also acting against compartmentalized virus in these tissues? Are there ways we can focus the immune response on virus replicating in the gut? And perhaps most importantly, are there lessons from other diseases of the gut that could provide clues about fighting HIV/SIV at mucosal surfaces?
Our SIV pathogenesis projects are funded by NIH NIAID, with additional funding for the mucosal projects pending.