Extracellular vesicles produced by HIV-infected cells pass along the infection.
Researchers have discovered that the human immunodeficiency virus (HIV) uses nano-sized vesicles released by virus-infected cells, to infect new cells.
The bubble-like structures comprised of many cells, extracellular vesicles (EVs), are produced and used by HIV-infected cells to pass along the infection, according to the study by National Institutes of Health researchers.
Senior author Leonid Margolis, PhD — of the Section of Intercellular Interactions at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development – said the removal of EVs from HIV laboratory preparations could reduce the virus infection of human tissues in culture.
“Therapies that target extracellular vesicles could potentially hinder the ability of the virus to infect new cells,” Margolis said.
A primary function of EVs is to transport molecules from one cell to another, providing a form of communication. The EVs produced and used by HIV-infected cells ae believed to be formed in a way similar to how a virus forms.
Structures form at the infected cell’s outer membrane, before the part of the membrane nearest to the surface pinches off and creates a spherical discrete separate from the cell. The HIV-infected EVs contain RNA.
Researchers used a new technology to study the extremely small EVs — which are generally difficult to sort with conventional methods. Using antibodies chemically attached with magnetic nanoparticles, they connected the antibodies to a target molecule on the EV or virus’ surface, then pulled the subject out of solution with magnetic forces.
The EVs and HIV take many proteins found in the cell membrane with them when released by cells, Margolis said. But EVs carry the protein CD45 and the enyme acetylcholinesterase, while HIV does not. The researchers were able to pull EVs out of laboratory preparations of HIV, and found that EVs produced by HIV-infected cells also carry the HIV protein gp120 — which HIV uses to bind to cells during infection.
After adding the EV-removed samples to blocks of human lymphatic tissue, researchers found the HIV infections in the culture were 55 percent lower when compared to EV-retained control samples.
Researchers believe the removal of gp120 was responsible for the drop in HIV infection.
Though EVs lack the HIV RNA to infect a cell, researchers believe the gp120 on the EV surface can interact with the host cell, allowing HIV to infect it more easily.
Other authors of the study includes the NICHD Section on Intercellular Interactions’ Anush Arakelyan, PhD, Wendy Fitzgerald, PhD, and Christophe Vanpouille, PhD.
The study, "Extracellular vesicles carry HIV ENV and facilitate HIV infection in lymphoid tissue,” was published in Scientific Reports this year.
A press release regarding the study was made available.