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A subgroup of Ugandan elite and viremic controllers naturally control HIV-1 infection by blocking R5-tropic viral entry.

A subgroup of Ugandan elite and viremic controllers naturally control HIV-1 infection by blocking R5-tropic viral entry.

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dc.contributor.author Alex Kayongo
dc.contributor.author Derrick Semugenze
dc.contributor.author Mary Nantongo
dc.contributor.author Fred Semitala
dc.contributor.author Anxious Jackson Niwaha
dc.contributor.author Robert Kalyesubula
dc.contributor.author Bruce Kirenga
dc.contributor.author Bernard Sentalo Bagaya
dc.contributor.author Moses Lutaakome Joloba
dc.date.accessioned 2021-01-11T13:51:40Z
dc.date.available 2021-01-11T13:51:40Z
dc.date.issued 2020
dc.identifier.uri https://combine.alvar.ug/handle/1/49431
dc.description.abstract Abstract; Background: World over, there are antiretroviral therapy naïve individuals infected with HIV who maintain their CD4+T cell count above 500 cells/µl over 7-10 years and viral loads well controlled below undetectable levels (termed elite controllers, ECs) or at least 2,000 copies/mL (termed viremic controllers, VCs) for at least 12 months. Mechanisms responsible for HIV control in these individuals have not been fully elucidated. We hypothesized that CD4+T cells from elite and viremic controllers are naturally resistant to HIV-1 infection by blocking R5-tropic viral entry. We conducted a case-controlled study in which archived peripheral blood from 31 ECs/VCs and 15 progressors were investigated using in vitro HIV-1 infectivity assays. Results: Briefly, we purified CD4+T cells from peripheral blood using EasySep CD4+ positive selection kit followed by CD4+T cell activation using IL-2, anti-CD28 and anti-CD3. Three days post-activation, CD4+T cells were spinoculated and co-cultured with vesicular stomatitis virus G (VSV-G)-pseudotyped HIV, R5 (ADA-enveloped)- and X4 (NL4.3-enveloped v)-tropic HIV-1. Three days post infection, we quantified and compared the percentage infection of CD4+T cells in cases and controls. We demonstrate that a subgroup of Ugandan elite and viremic controllers possess CD4+T cells that are specifically resistant to R5-tropic virus, remaining fully susceptible to X4-tropic virus. Conclusion: Our study suggests that a subgroup of Ugandan elite and viremic controllers naturally control HIV-1 infection by blocking R5-tropic viral entry. Further research is needed to explore mechanisms of HIV control in the African population.
dc.publisher Research Square
dc.title A subgroup of Ugandan elite and viremic controllers naturally control HIV-1 infection by blocking R5-tropic viral entry.
dc.type Preprint
dc.identifier.doi 10.21203/rs.3.rs-86395/v1
dc.identifier.lens 016-155-124-976-863


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