HIV Infection and Persistence in Pulmonary Mucosal Double Negative T Cells In Vivo

Author:

Meziane Oussama12,Salahuddin Syim12,Pham Tram N. Q.3,Farnos Omar2,Pagliuzza Amélie4,Olivenstein Ron5,Thomson Elaine126,Alexandrova Yulia126,Orlova Marianna17,Schurr Erwin17,Ancuta Petronela48,Haddad Élie8910,Chomont Nicolas48,Cohen Eric A.38ORCID,Jenabian Mohammad-Ali268ORCID,Costiniuk Cecilia T.1611ORCID

Affiliation:

1. Infectious Diseases and Immunity in Global Health, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada

2. Department of Biological Sciences, Université du Québec à Montréal, Montreal, Quebec, Canada

3. Institut de Recherches Cliniques de Montréal, Montreal, Quebec, Canada

4. Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montreal, Quebec, Canada

5. Division of Respirology, Department of Medicine, McGill University, Montreal, Quebec, Canada

6. Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada

7. Department of Human Genetics, McGill University, Montreal, Quebec, Canada

8. Département de microbiologie, infectiologie et immunologie, Université de Montréal, Montreal, Quebec, Canada

9. Research Center of CHU Sainte-Justine, Montreal, Quebec, Canada

10. Department of Pediatrics, Université de Montréal, Montreal, Quebec, Canada

11. Division of Infectious Diseases and Chronic Viral Illness Service, McGill University Health Centre, Montreal, Quebec, Canada

Abstract

Reservoirs of HIV during ART are the primary reasons why HIV/AIDS remains an incurable disease. Indeed, HIV remains latent and unreachable by antiretrovirals in cellular and anatomical sanctuaries, preventing its eradication. The lungs have received very little attention compared to other anatomical reservoirs despite being immunological effector sites exhibiting characteristics ideal for HIV persistence. Furthermore, PLWH suffer from a high burden of pulmonary non-opportunistic infections, suggesting impaired pulmonary immunity despite ART. Meanwhile, various immune cell populations have been proposed to be cellular reservoirs in blood, including CD4 CD8 DN T cells, a subset that may originate from CD4 downregulation by HIV proteins. The present study aims to describe DN T cells in human and humanized mice lungs in relation to intrapulmonary HIV burden. The characterization of DN T cells as cellular HIV reservoirs and the lungs as an anatomical HIV reservoir will contribute to the development of targeted HIV eradication strategies.

Funder

Canada Research Chairs

Gouvernement du Canada | Canadian Institutes of Health Research

Fonds de Recherche du Québec - Santé

McGill University Health Centre

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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