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Two autopsies reveal where HIV hides

Canadian researchers have identified the organs in which the HIV virus prefers to hide, thanks to two men who were on ARVs – and at the end of their lives – and who donated their bodies to medical science.

A small number of HIV-infected cells remain in the tissues of people living with the virus and who are undergoing antiretroviral therapy – these viral reservoirs, real obstacles to the cure of HIV, having long been known to exist.

Until now, however, it wasn’t known in which organs the virus prefers to hide.

The team from the Canadian HIV Cure Enterprise (CanCure), led by Université de Montréal immunology professor Nicolas Chomont, a researcher at the CHUM Research Centre (CRCHUM), succeeded in identifying these hidden places, opening the way to targeting them for future therapies.

In their study, published in the journal Cell Reports, the scientists reveal that genetically intact viruses, responsible for viral rebound if antiretroviral therapy is interrupted, are concentrated in the deep tissues of the spleen and lymph nodes, organs of the immune system.

“We owe these results first and foremost to the generosity of two Canadian men who by donating their bodies to science, made a unique contribution to our work. It is extremely rare to have access to post-mortem analysis for the presence or absence of viral reservoirs in so many organs of the same human body – about 15, in this case,” said Chomont.

Mapping human reservoirs

Caroline Dufour, a doctoral student in Chomont’s laboratory at the CRCHUM and the lead author of this study, developed ultra-sensitive methods of analysis to locate the body’s preferred hiding places for viral reservoirs.

Using a protocol for analysing the few viral genomes persisting in tissues, she was able to identify the organs in which “live” HIV preferentially hides.

“In the one donor, genetically intact viruses were concentrated in the lymph nodes and spleen,” said Chomont. “In the tissues of the other participant, they were found predominantly in the same organs, although lower concentrations could also be detected in other tissues.”

Potential window of opportunity

Thanks to her analyses, Dufour was also able to demonstrate that distant organs, such as the cells of an axillary ganglion (in the armpit) and those of an inguinal ganglion (in the groin), could harbour identical intact HIV genomes.

“This finding suggests that the infected cells harbouring these ‘dormant’ viruses have the ability to travel throughout the body and to change organs, even with antiretroviral therapy in place,” said Chomont. “The reservoir is therefore very dynamic, much more so than we had thought.”

This recirculation of infected cells in the body provides an undeniable therapeutic advantage. Away from their deep tissue hiding places, they are now more readily visible to the immune system and thus susceptible to attack and subsequent elimination.

Chomont’s team currently holds tissue samples from a third Canadian donor. The team is counting on further body donations to launch analyses aimed at determining specifically in which part of the body the virus is most active.

Study details

Near full-length HIV sequencing in multiple tissues collected post-mortem reveals shared clonal expansions across distinct reservoirs during ART

Caroline Dufour, Maria Julia Ruiz, Amélie Pagliuzza,  Éric A. Cohen, Nicolas Chomont, et al.

Published in Cell Reports on 6 September 2023

Highlights
• In people on ART, half the HIV genomes in tissues are clonally expanded
• Genetically intact HIV proviruses are more often found in lymphoid tissues
• Identical proviral sequences are frequently found in distant tissues

Summary
HIV persists in tissues during antiretroviral therapy (ART), but the relative contribution of different anatomical compartments to the viral reservoir in humans remains unknown. We performed an extensive characterisation of HIV reservoirs in two men who donated their bodies to HIV cure research and who had been on suppressive ART for years. HIV DNA is detected in all tissues, with large variations across anatomical compartments and between participants. Intact HIV genomes represent 2% and 25% of all proviruses in the two participants and are mainly detected in secondary lymphoid organs, with the spleen and mediastinal lymph nodes harboring intact viral genomes in both individuals. Multiple copies of identical HIV genomes are found in all tissues, indicating that clonal expansions are common in anatomical sites. The majority (>85%) of these expanded clones are shared across multiple tissues. These findings suggest that infected cells expand, migrate, and possibly circulate between anatomical sites.

 

Cell Reports article – Near full-length HIV sequencing in multiple tissues collected post-mortem reveals shared clonal expansions across distinct reservoirs during ART (Creative Commons Licence)

 

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