Sugar-Based Signature Can Identify Persistent HIV Reservoirs

A sugar-based signature can identify T cells with hidden HIV viral deposits during antiretroviral therapy (ART), according to a new study published in Cell Reports.

ART has helped to increase the health and longevity of patients living with HIV. The therapy suppresses virus replication in host immune cells, which stops disease progression, according to the study.

However, despite treatment with ART, a small, persistent amount of the virus remains in blood and tissues, which contributes to the ability of HIV to hide in a rare population of CD4 T cells. This limits immune recovery and is associated with chronic inflammation, which puts the patient at a higher risk of developing certain diseases, according to the study.

Cells that are persistently infected despite treatment can be sorted in 2 groups. In the first group, the virus does not produce any RNA, making it completely silent. The other groups are cells in which the virus produces low levels of RNA, making it an active HIV reservoir, according to the study. It is important that researchers find a way to target and eliminate both kinds of cells in order to eradicate the virus, the study authors noted.

The study used a primary cell model of HIV latency in order to characterize the cell surface glycomes of HIV-infected cells. The researchers found that a process known as fucosylation was taking place in persistently infected T cells in which the virus is being actively transcribed. Fucosylation is when a sugar molecule attaches to proteins on the surface of the T cell, which is critical for activation.

The study also identified a fucosylated antigen known as SialylLewis X (SLeX), which identifies HIV transcription in vivo. This pattern was not found in HIV-infected cells in which the virus is inactive. This can provide a distinguishing factor between cells that are an active HIV reservoir and those that are completely silent.

"With recent advances that we are making in the fields of glycobiology and glycoimmunology, it has become clear that the sugar molecules present on the surface of immune cells play a critical role in regulating their functions and fate…However, the relevance of host cell-surface glycosylation in HIV persistence remained largely unexplored, making it a 'dark matter' in our understanding of HIV latency. For the first time, we described a cell-surface glycomic signature that can impact HIV persistence,” corresponding author and assistant professor in The Wistar Institute Vaccine & Immunotherapy Center, Mohamed Abdel-Mohsen, PhD, said in the press release.

SLeX is involved in the trafficking between blood and tissues, and the different levels may play a role in the persistence of HIV in tissues, according to the study. Further studies are needed to determine how fucosylation can be used to target HIV reservoirs in tissues and blood.

Reference:

Sugar-based signature identifies T cells where HIV hides despite antiretroviral therapy (News Release) Philadelphia, PA, August 4, 2020, EurekAlert! Accessed August 17, 2020