Research Refutes CD32 as HIV Latent Reservoir Marker

APRIL 18, 2018
Jenna Payesko
Luis Montaner, DVM, D.Phil, director, HIV-1 Immunopathogenesis Unit, The Wistar Institute Vaccine and Immunotherapy CenterLuis Montaner, DVM, D.Phil
CD32, a molecule that was first identified as a preferential biomarker to differentiate dormant HIV-infected cells from healthy cells within the immune system of patients undergoing antiretroviral therapy (ART) is being refuted.

Spearheaded by The Wistar Institute in collaboration with the University of Pennsylvania and Vall d’Hebron Research Institute, researchers, after exploring the first report, disproved that the CD32 molecule is not a preferential biomarker to identify HIV silent reservoirs, but instead discovered that CD32 identifies cells actively infected in spite of ART.

“‘It’s not like it’s not telling us anything, but it’s not telling us what the report initially suggested,” lead corresponding author, Luis Montaner, DVM, D.Phil, director, HIV-1 Immunopathogenesis Unit, The Wistar Institute Vaccine and Immunotherapy Center, told MD Magazine. “We’ve gained information about how best to use this marker, like other activation markers, that we already know are associated with a cell that may be transcriptionally active in expressing HIV.”

According to Montaner, one the main obstacles in trying to cure HIV is attempting to isolate and identify HIV in those otherwise under ART but where the virus persists in reservoir cells.

Researchers thoroughly analyzed blood and immune tissues from HIV-negative donors, HIV-positive individuals treated with ART and HIV-positive viremic from many institutions around the world. Similar findings were also observed in an animal model of HIV infection.

The new report indicated that CD32 did not enrich for HIV DNA—a main trait of latently infected cells—but instead, pointed to a direct link between CD32 expression and active HIV infection—suggested by the concomitant presence of HIV RNA.

Additionally, CD32 expression is refuted as rather a marker for activated, HIV infected CD4 T cells, since it was co-expressed with other molecules that characterized immune activation.

“We can use this even if it accounts for a small percentage of the reservoir,” Montaner noted. “Original reports account for a larger enrichment of HIV DNA, but we actually found that it accounted for less—about 3% of the HIV DNA you have there. So, it wasn’t an enrichment, but it was actually a minor population of entire amount that was measured, however, it does tell us about the active transcribed HIV, so we can use that, to perhaps understand what maintains a small amount the virus expressed.”

Researchers did not set out to disprove the previously reported findings published in Nature, but to incorporate the findings in additional studies targeting HIV, which led to the initial introduction into the line of investigation. In an attempt to broaden and utilize the original results, researchers concluded the findings were different from the original report—challenging the idea that CD32 identifies HIV latently infected T cells.

“From the point of view of the reservoir, we still are where we were before the report came out,” Montaner concluded. “We still need to identify what markers could potentially give us the strategy to identify the latent reservoir, and we proved that CD32 is not it.”

The research article, "CD32 is expressed on cells with transcriptionally active HIV but does not enrich for HIV DNA in resting T cells" was published in Science Translational Medicine.

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