MedicalResearch.com Interview with:
Manish Sagar, MD
Infectious Disease Physician at Boston Medical Center
MedicalResearch.com: What is the background for this study?
Response: Women compromise the majority of new infections in the world and most of them acquire the virus after sexual exposure. The goal of the study was to understand how HIV establishes initial infection in the female genital tract. We obtained discarded vaginal tissue and isolated cells present in the outermost layer that contact the virus during exposure.
MedicalResearch.com: What are the main findings?
Response: We found that the outermost epithelial cells, termed vaginal epithelial dendritic cells, were unique compared to other previously known cell types present in the blood and other epithelia commonly used in HIV studies. We further found that HIV was able to replicate in these vaginal epithelial dendritic cells and the types of viruses known to initiate infections replicated more efficiently compared to the general non-transmitted variants.
Finally, we found HIV DNA in vaginal epithelial dendritic cells isolated from two women who were HIV infected but successfully treated with antiretroviral drugs.
In summary, our studies suggest that the vaginal epithelial dendritic cells that we isolated have not previously been characterized. Their characterization suggests that they may be the first cell that is infected during sexual exposure, and these cells may retain virus even after treatment. Thus, these cells are important for HIV transmission and persistence.
MedicalResearch.com: What should readers take away from your report?
Response: Our studies suggest that vaginal epithelial dendritic cells may be the initial cell that is infected after women are exposed to the virus during sexual contact. In the absence of a HIV vaccine, developing novel ways to prevent infection of vaginal epithelial dendritic cells may eliminate sexual transmission to women.
We know that HIV DNA exists in infected individuals indefinitely. Our finding that HIV DNA is found in vaginal epithelial dendritic cells suggest that these cells are also one reason why HIV can persist forever even with effective treatment. This study may possibly lead to a female specific prevention drug; stopping infection of vaginal epithelial dendritic cells may prevent acquisition.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: We are starting to explore if there are similar cells in foreskins. This is important because it has been well documented that circumcision reduces risk of HIV acquisition. We hypothesize that circumcision eliminates the epithelial dendritic cells and thus HIV transmission is lower.
J Clin Invest. 2018 May 3. pii: 98943. doi: 10.1172/JCI98943. [Epub ahead of print]
HIV-1 replicates and persists in vaginal epithelial dendritic cells.
Pena-Cruz V, Agosto LM, Akiyama H, Olson A, Moreau Y, Larrieux JR, Henderson A, Gummuluru S, Sagar M.
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