HIV infection mediates a progressive and irreversible depletion of CD4+ T-cells leading to immunodeficiency. Although it is clear that the loss of CD4+ T-cells is restricted to uninfected bystander cells; the mechanism via which HIV mediates this phenomenon is unknown. The Env glycoprotein of HIV-1 has been implicated in mediating bystander cell death via a variety of mechanisms. The role of the gp41 subunit in mediating bystander cell death is becoming increasingly evident and is supported by the fact that Env fusogenic activity has been correlated with pathogenicity both in vitro and in vivo.
Dr. Garg's long standing interest has been in studying the role of HIV Env glycoprotein and more specifically the fusogenic activity of the Env glycoprotein and how it determines HIV pathogenesis. He previously demonstrated that hemifusion mediated by HIV gp41 is a prime mediator of bystander apoptosis and that some gp41 mutations that are seen in HIV-infected patients undergoing Enfuvirtide therapy are attenuated for bystander apoptosis. Dr. Garg demonstrated in studies with humanized mice and a fusion defective gp41 mutant that bystander apoptosis induction in the humanized mouse model is dependent on gp41 function. Dr. Garg also showed that the phenomenon of bystander apoptosis is dependent on CCR5 expression level as well as gp41 fusion. His studies provide the first experimental evidence for the reason why CCR5Δ32 individuals progress slowly to AIDS.
While experimental evidence supports the idea that Env mediated damage of bystander cells maybe one of the contributing factors in HIV disease progression, the clinical relevance of these findings remains largely untested. It is well known that Env is the most variable of all of the HIV genes. Whether this variability in the Env gene affects bystander apoptosis inducing activity in patients in vivo and whether this aspect correlates with disease progression and/or HIV pathogenesis remains undetermined. The Garg Lab aims to study the bystander apoptosis inducing potential of envelope clones from HIV infected patients and its association with AIDS pathogenesis.
Besides HIV, Dr. Garg's lab is also interested in developing a virus-like particle vaccine and neutralization assay for Dengue virus and development of novel Influenza virus vaccines designed to protect against emerging influenza.
Dr. Garg obtained his Ph.D. in Immunology from the College of Veterinary Medicine at North Carolina State University. He completed his post-doctoral training in the lab of Dr. Robert Blumenthal at the National Cancer Institute of NIH before joining TTUHSC El Paso.
View Dr. Garg's publications at Pubmed.