HIV Infection of Macrophages: Implications for Pathogenesis and Cure

Kiera Leigh Clayton,Bruce D Walker,Janice E Clements,Victor Garcia

doi:10.20411/10.20411/pai.v2i2.204

Kiera Leigh Clayton, Bruce D Walker + Show 2 more

Open Access

https://doi.org/10.20411/10.20411/pai.v2i2.204

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Abstract

Although CD4+ T cells represent the major reservoir of persistent HIV and SIV infection, accumulating evidence suggests that macrophages also contribute. However, investigations of the role of macrophages are often underrepresented at HIV pathogenesis and cure meetings. This was the impetus for a scientific workshop dedicated to this area of study, held in Cambridge, MA in January 2017. The workshop brought together experts in the fields of HIV/SIV immunology/virology, macrophage biology and immunology, and animal models of HIV/SIV infection to facilitate discussions regarding the role of macrophages as a physiologically relevant viral reservoir, and the implications of macrophage infection for HIV pathogenesis and cure strategies. An emerging consensus that infected macrophages likely persist in the setting of combination antiretroviral therapy, driving persistent inflammation and contributing to the viral reservoir, indicate the importance of addressing macrophages as well as CD4+ T cells with future therapeutic strategies.

Highlights

CD4+ T cells represent the major reservoir of persistent HIV and SIV infection, accumulating evidence suggests that macrophages contribute
Persistent inflammation remains a problem despite combination antiretroviral therapy (cART), driving ongoing disease pathogenesis, and the prospect of life-long therapy due to persistent viral reservoirs is a medical, economic, and social challenge
CONCLUDING SESSION: SETTING RESEARCH PRIORITIES Concluding the meeting was a session led by Dr Dan Kuritzkes (Brigham and Women’s Hospital, MA), Dr Jeymohan Joseph (NIMH, MD) and Dr Diane Lawrence (NIH/NIAID, MD), with contributions from Dr Jim Demarest (ViiV Healthcare)

Summary

Introduction

CD4+ T cells represent the major reservoir of persistent HIV and SIV infection, accumulating evidence suggests that macrophages contribute. The major focus of the workshop was the interaction of HIV/SIV with macrophages, reservoir persistence, immune evasion, and the development of new technologies to characterize infected macrophages ex vivo and in vivo. Dr Deeks emphasized that while the human macrophage contribution to the HIV reservoir requires further investigation, monocytes and macrophages clearly contribute to chronic inflammation, especially in the brain, in HIV-infected individuals.

Results

Conclusion