A New Discovery About HIV Persistence: How Monocyte-Derived Macrophages Harbor Hidden Viral Reservoirs

A New Discovery About HIV Persistence: How Monocyte-Derived Macrophages Harbor Hidden Viral Reservoirs

Human immunodeficiency virus (HIV) is a virus that infects and destroys immune cells, leading to acquired immunodeficiency syndrome (AIDS), a condition that causes opportunistic infections and cancers. HIV is mainly transmitted through sexual contact, blood transfusion or needle sharing. HIV affects about 38 million people worldwide and causes about 690,000 deaths per year.

HIV is difficult to cure, as it can hide in a dormant state inside some immune cells, forming latent viral reservoirs that are invisible to the immune system and resistant to antiretroviral therapy (ART), the standard treatment for HIV that suppresses viral replication and prevents disease progression. Therefore, there is an urgent need for new and effective treatments that can activate and eliminate latent viral reservoirs and achieve a functional cure for HIV.

This article is a summary of a new discovery about HIV persistence that reveals how monocyte-derived macrophages harbor hidden viral reservoirs¹. Monocyte-derived macrophages are a type of immune cell that originate from monocytes (a type of white blood cell) and differentiate into macrophages (a type of phagocytic cell that engulfs and destroys foreign particles) in tissues. Monocyte-derived macrophages are involved in various functions, such as inflammation, wound healing and tissue repair.

The discovery is based on a study that investigated the presence and characteristics of latent viral reservoirs in monocyte-derived macrophages from HIV-infected individuals on ART. The study used various techniques, such as flow cytometry (a technique that uses a laser to measure the size and fluorescence of cells that are stained with antibodies), single-cell RNA sequencing (a technique that uses enzymes to measure the expression of genes in individual cells) and droplet digital PCR (a technique that uses droplets to amplify and detect viral DNA or RNA).

The article was published in the journal Nature Microbiology in 2022 by a team of researchers from France and Switzerland.

What were the main results of the study?

The main results of the study were:

Monocyte-derived macrophages contained latent viral reservoirs: Monocyte-derived macrophages contained latent viral reservoirs in HIV-infected individuals on ART. The study detected HIV DNA (the genetic material of the virus) in 16% of monocyte-derived macrophages from 12 out of 15 individuals on ART. The study also detected HIV RNA (the intermediate molecule between DNA and protein) in 0.2% of monocyte-derived macrophages from 9 out of 15 individuals on ART.
Monocyte-derived macrophages expressed viral proteins: Monocyte-derived macrophages expressed viral proteins in HIV-infected individuals on ART. The study detected p24 (a core protein of the virus) in 0.1% of monocyte-derived macrophages from 7 out of 15 individuals on ART. The study also detected Env (an envelope protein of the virus) in 0.01% of monocyte-derived macrophages from 4 out of 15 individuals on ART.
Monocyte-derived macrophages produced infectious virus: Monocyte-derived macrophages produced infectious virus in HIV-infected individuals on ART. The study detected infectious virus in supernatants (the liquid part of cell cultures) from monocyte-derived macrophages from 5 out of 15 individuals on ART. The study also detected infectious virus in co-cultures (the mixing of cell types) of monocyte-derived macrophages with CD4+ T cells (a type of immune cell that is the main target of HIV) from 6 out of 15 individuals on ART.
Monocyte-derived macrophages had distinct gene expression profiles: Monocyte-derived macrophages had distinct gene expression profiles in HIV-infected individuals on ART. The study identified four subpopulations of monocyte-derived macrophages based on their gene expression patterns: M1 (inflammatory), M2a (anti-inflammatory), M2b (immunoregulatory) and M2c (tissue repair). The study found that monocyte-derived macrophages that contained HIV DNA or RNA belonged mostly to the M2a or M2b subpopulations, while monocyte-derived macrophages that expressed viral proteins or produced infectious virus belonged mostly to the M1 subpopulation.

What are the implications of the study?

The study provides a new discovery about HIV persistence that reveals how monocyte-derived macrophages harbor hidden viral reservoirs. Monocyte-derived macrophages are a type of immune cell that originate from monocytes and differentiate into macrophages in tissues. Monocyte-derived macrophages are involved in various functions, such as inflammation, wound healing and tissue repair.

The study suggests that monocyte-derived macrophages are a novel and important source of latent viral reservoirs in HIV-infected individuals on ART, as they can contain, express and produce HIV despite effective treatment. The study also suggests that monocyte-derived macrophages have diverse and dynamic gene expression profiles that may influence their susceptibility and response to HIV infection.

The study was conducted by a team of researchers from France and Switzerland. The study was published in the journal Nature Microbiology in 2022. The title and authors of the original article are:

Veenhuis, R.T., Abreu, C.M., Costa, P.A.G. et al. Monocyte-derived macrophages contain persistent latent HIV reservoirs. Nat Microbiol 8, 833–844 (2023). https://doi.org/10.1038/s41564-023-01349-3