HIV researchers have been trying to figure out which cells the virus likes to hide in. The memory CD4 T cells are a type of immune cells favored by HIV. It has been difficult to determine what makes one type of CD4 T cell more attractive to HIV than another.
The question of whether CD4 T cells have a collection of proteins on their surface has been asked for years by a team of investigators led by the associate investigator. They were able to see sugars at the cell's surface.
Mohamed Abdel-Mohsen is a specialist in the cellular machinery that makes sugars. The scientists discovered sugar patterns on different immune cells and an interplay between HIV and sugars on CD4 T cells. The journal e Life has their findings.
The amount of a single type of surface sugar can distinguish between memory CD4 T cells with vastly different biological features and susceptibility to HIV.
A new technique for studying individual cells from large populations could lead to a better picture of cellular diversity.
Abdel-Mohsen says there is a lot of cell surface sugars. They have been under studied because they are hard to track. By sorting large populations of cells based on their sugar andprotein profiles, we may uncover new classes of cells that have not been discovered before and could hold the key to solving important biological problems.
The sugars coat individual cells.
The researchers looked at the sugar molecule. There are a number of cell properties that can be affected by the types of sugars in the chains.
"We wondered to what extent cell- surface sugars might help us tell apart different types of cells within a population of immune cells," says Tongcui Ma, the study's first author.
The team used a technique called CyTOF to answer the question. CyTOF can record the presence, absence, and amount of nearly 40 different genes at once. Five of the CyTOF antibodies were replaced with five different lectins that could recognize different types of sugars.
Abdel-Mohsen says that they don't have as many lectins. We plan to expand our work by using new lectins in the future, because we know of several lectins that can distinguish between a variety of sugars.
The scientists analyzed immune cells from the blood and tissues of donors. Blood, tonsil, and the reproductive tract were found to have different patterns of sugars.
"We now have a good toolkit to analyze in great detail the combination of the two sugars present on a single cell." Since all cells in the body have sugars at their surface, we believe CyTOF-Lec will be useful.
HIV's toothy grin.
The scientists applied CyTOF-Lec to the CD4 T cells that they had first exposed to HIV. Not all CD4 T cells become HIV positive, and Roan's team and others have been able to identify the most vulnerable cells.
The scientists know that after HIV enters a cell, it makes changes to the cell's surface. PP-SLIDE is a tool that is used to reconstruct the profile of a cell before it becomes HIV positive.
The team made two discoveries with the combination of CyTOF-Lec and PP-SLIDE.
The CD4 T cells have the largest amounts of two types of sugars on their surface. Studies have shown that one of these sugars, sialic acid, is needed for HIV to work.
HIV increased the production of the two sugars in the cells it had invaded.
There seem to be multiple mechanisms to ensure high levels of sialic acid oninfecting cells, and it is intriguing that HIV's bias towards cells with a lot of sialic acid, and its ability to further increase surface sialic acid amounts, seem to be the ones that Since sialic acid is associated with evasion from the immune system, this may help HIV-infecting cells survive.
The stealth cells may allow HIV to quickly take hold and spread to more places in the body. Good therapeutic targets may be represented by them.
HIV hides from immune defenses by hiding in some cells. The silent cells are difficult to eradicate because they can't be distinguished from the non-infecting cells. The CyTOF-Lec will be applied to samples from people living with HIV in order to see if the cells persist even in the presence of antiretroviral therapy.
"In doing so, we might discover sugar-based markers that could be used to target and eliminate the cells that are infectious."
More experiments will need to be done to test these hypotheses. The CyTOF-Lec is a promising new tool to uncover new cell biology, including the role of sugars in infections other than HIV.
More information: Tongcui Ma et al, Single-cell glycomics analysis by CyTOF-Lec reveals glycan features defining cells differentially susceptible to HIV, eLife (2022). DOI: 10.7554/eLife.78870 Journal information: eLife
All Rights Reserved © 2024
