Glycomic approaches to understanding HIV-1 budding in T cells

The causative agent of AIDS (acquired immune deficiency syndrome), HIV (human immunodeficiency virus), is one of the most extensively studied pathogens in modern history. The virus has multiple mechanisms of persisting in the host including evading host immune response. Since HIV-1 depends heavily on the host machinery for various aspects of its life cycle, unraveling the complex interplay between the host and HIV-1 could provide new clues to therapeutic avenues. In T cells, HIV assembles and subsequently buds through the plasma membrane incorporating host derived proteins and lipids in the viral envelope. HIV is thought to utilize a pre-existing mechanism for the budding of normal cellular vesicles called microvesicles to exit host cells. The evidence for this theory comes from reports of similarities between HIV and microvesicles observed for a small subset of proteins and lipids, leading to controversies about its validity. To further test this hypothesis, we utilized lectin microarrays to obtain a comprehensive glycomic profile of HIV and microvesicles derived from a panel of T cell lines. Glycosylation is critical to protein sorting and has a crucial role in HIV-1 biology, making it an ideal marker to compare the particles and the host cell membrane. We observed similar glycomic profiles for HIV-1 and microvesicles strongly suggesting an analogous mode of egress. Glycosylation of both particles seems to vary based on the parent cell line, providing additional evidence for this hypothesis. Microvesicles are involved in immune response modulation; hence the incorporation of microvesicular proteins could influence interactions of HIV with the immune system. The differences in glycosylation between these two particles could be potentially explained by the heavily glycosylated viral envelope glycoprotein. I also demonstrated that these vesicles bud from particular glycan enriched domains of the plasma membrane. Additionally, this work sheds light on the potential mode of interaction between galectin, an immune lectin and HIV-1. This work strongly argues for a conserved mechanism of exocytosis for both particles and sets the stage for examining the role of glycosylation in trafficking of proteins to the sites of microvesicular and viral budding.