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Publications of the Week

Mechanisms of Endogenous HIV-1 Reactivation by Endocervical Epithelial Cells

By February 20, 2020No Comments

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This week we profile a recent publication in the Journal of Virology from the laboratory of Dr. Florian Hladik (pictured) at UW.

Can you provide a brief overview of your lab’s current research focus?

Currently, my laboratory’s research focuses on the mechanisms sustaining the latent HIV reservoir, improving our technologies to quantify reservoir size, and developing and testing new treatments to eradicate the HIV reservoir, especially by limiting the division of latently infected cells. We are also interested in determining the role of certain antiretroviral drugs in chronic immune activation, long-term morbidities in people living with HIV, and, paradoxically, sustainment of the latent HIV reservoir. In other studies, such as the one just published in the Journal of Virology, we aim to define how, and where in the body, HIV reactivates when antiretroviral treatment is stopped. Aside from HIV, we work on the pathogenesis of sexual Zika virus transmission, the biological effects of extracellular vesicles in semen on immunity in the receiving female genital tract, the effect of opioids on germline cells in men, and the mechanisms of immunological tolerance during pregnancy.

What is the significance of the findings in this publication?

The significance is the demonstration that the immunological activities of certain epithelial cells, in this case located in the endocervical canal of the human uterus, can trigger HIV reactivation from bystander T cells. This is important because once we have effective HIV eradication therapies in place (which is not yet the case), we will need to prevent HIV reactivation from remaining latently infected cells when such treatment is stopped. We believe that the mechanisms we uncovered with endocervical epithelial cells likely apply to other locations in the body as well, especially the gastrointestinal tract.

What are the next steps for this research?

In this particular line of research, we want to extend our studies (1) from model cell lines of HIV reactivation to latently infected T cells from patients, (2) from T cells to latently infected macrophages, which likely contribute to the latent HIV reservoir but are often neglected in research, (3) from endocervical epithelial cells to epithelial cells lining the intestinal tract, (4) to define immunological factors other than TNF-alpha that lead to HIV reactivation, and (5) to test experimental treatments to prevent HIV reactivation.

This work was funded by:

I would like to thank the National Institute for Allergy and Infectious Diseases and the National Institute on Drug Abuse for funding our research.

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