Are Follicular Helper T Cells Viral Reservoirs for HIV-2?

Follicular helper T cells (Tfh) support productive HIV-2 infection, are key viral reservoirs for HIV-2, and are preferential viral targets among individuals with HIV-2, according to results of a new study.

To analyze Tfh susceptibility to HIV-2 infection, the researchers combined in-vitro infection of tonsillar Tfh with the ex-vivo study of circulating Tfh from patients with HIV-2. 

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To conduct the study, tonsil specimens were obtained through routine pediatric tonsillectomy performed at a hospital in Portugal. Tfh were then isolated from the tonsillar mononuclear cells.

“We found that HIV-2 were able to infect Tfh, irrespectively of coreceptor usage as shown by total HIV DNA levels measured after 24 hours of infection,” the study authors wrote.

By quantifying viral gag mRNA after 24 hours of infection, the levels of viral transcription in HIV-2-infected Tfh were also assessed. Ongoing viral transcription in HIV-2-infected Tfh was found, as determined by the R5- and X4-tropic HIV-2 viruses both having generated gag mRNA transcripts.

Because it was determined that differentiated Tfh are susceptible to R5-tropic viruses, the researchers confirmed that low levels of CCR5 are enough for efficient HIV-1 and HIV-2 infection.

And unlike in HIV-1 infection, there was a significant direct correlation between the levels of total HIV DNA and gag mRNA in HIV-2-infected Tfh.

“Our results, taken together, show that Tfh support productive HIV-2 infection and represent a key HIV-2 reservoir,” the researchers concluded. “Thus, HIV-2 infection of Tfh provides a unique model to identify host factors playing a role in the natural control of HIV-2 replication and to further investigate the generation of HIV nAbs.”

—Colleen Murphy

Reference:

Godinho-Santos A, Foxall RB, Antão AV, et al. Follicular helper T cells are major human immunodeficiency virus-2 reservoirs and support productive infection. J Infect Dis. 2020;221(1):122-126. https://doi.org/10.1093/infdis/jiz431.