Research Highlights

T cell glycoproteins: A sweet disguise for HIV

HIV daughter particles being shed from an infected T cell.

The human immunodeficiency virus (HIV) replication cycle has evolved in a way that makes it difficult for the immune system to detect and destroy the virus. HIV co-opts the host cell machinery to direct viral replication, becomes coated in host glycoproteins, and buds newly formed viruses from the cell membrane. The glycoprotein cloak not only hides the virus from immune detection, but has also thwarted many attempts to develop a vaccine. Despite this understanding, little is known about the exact composition of the host glycoproteins decorating the viral surface. Krishnamoorthy et al. address this gap in Nature Chemical Biology by showing that the HIV-1 and human T cell microvesicle glycomes are highly similar and depend on the cell line of origin.

Similar to viruses, immunomodulatory microvesicles bud from the plasma membrane of many cell types. In a lectin printed array each lectin recognizes and defines a different carbohydrate moiety on particle surfaces. Krishnamoorthy et al. used this system to compare the glycosylation patterns of T cell microvesicles and HIV-1 propagated in the same cell line, and found many similarities between HIV-1 and microvesicle glycopatterns. Both particles were enriched in high-mannose epitopes and other glycan structures that distinguished them from the host plasma membrane.

To determine whether these patterns were cell line-specific, the authors analyzed HIV-1 and microvesicles derived from two other T-cell lines. Consistent with their previous results, they found the particles shared glycopatterns, but differed from the plasma membrane of origin. However, the authors also discovered that glycopatterns of HIV and microvesicles derived from the same cell line were more similar to one another than HIV particles propagated in different cell lines.

Surprisingly, the lectin array experiments also exposed galectin-1 as one of the major lectins that bound to the high-mannose epitopes displayed by both particles. Galectin-1 is best known for binding glycan ligands that contain N-acetyllactosamine (LacNAc). However, the authors found that mannose inhibited HIV-galectin-1 binding better than lactose. Though unexpected, mining the glycan array data in the Consortium for Functional Glycomics (CFG) database revealed a precedent for galectin-1 binding to high mannose glycans. The authors speculate that the HIV glycoprotein gp120 could represent a HIV-1 surface galectin-1 target because it is high in mannose content.

Based on these findings, Krishnamoorthy et al. conclude that microvesicles and HIV-1 share a common cellular exit strategy involving specific microdomains of the plasma membrane defined by unique glycan content. By providing a cloak of host glycoproteins, this process enables HIV-1 to evade host immune clearance.

Author: Heather Buschman