Dataset Information

High levels of genetically intact HIV in HLA-DR+ memory T cells indicates their value for reservoir studies.

ABSTRACT:

Objective

The contribution of HLA-DR+ memory CD4 T cells to the HIV reservoir during prolonged antiretroviral therapy is unclear as these cells are commonly excluded when assessing for replication-competent HIV. To address this issue, we examined the distribution of genetically intact HIV DNA within HLA-DR- and HLA-DR+ memory CD4 T cells and the RNA transcriptional profile of these cells during antiretroviral therapy.

Design/methods

Full-length DNA sequencing was used to examine the HIV DNA landscape within HLA-DR+ and HLA-DR- memory CD4 T cells. RNA quantification and sequencing was used to interrogate the relationship between HLA-DR status and HIV RNA transcription.

Results

HLA-DR+ CD4 T cells contained a high frequency of genetically intact HIV genomes, contributing over half of the genetically intact viral sequences to the reservoir. Expansions of genetically identical sequences were identified in all T-cell subsets, indicating that cellular proliferation maintains genetically intact and defective viral DNA during therapy. Intracellular HIV RNA levels in HLA-DR+ and HLA-DR- T cells were not statistically different by either long terminal repeat quantitative PCR quantification or single-genome RNA sequencing of the p6-RT region.

Conclusion

The high proportion of intact viral DNA sequences in the proliferative HLA-DR+ subset suggests they are critical in maintaining HIV infection during effective therapy. As such, these cells should be included in any immune intervention targeting HIV during effective therapy.

SUBMITTER: Horsburgh BA

PROVIDER: S-EPMC7071960 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

High levels of genetically intact HIV in HLA-DR+ memory T cells indicates their value for reservoir studies.

Horsburgh Bethany A BA Lee Eunok E Hiener Bonnie B Eden John-Sebastian JS Schlub Timothy E TE von Stockenstrom Susanne S Odevall Lina L Milush Jeffrey M JM Liegler Teri T Sinclair Elizabeth E Hoh Rebecca R Boritz Eli A EA Douek Daniel C DC Fromentin Remi R Chomont Nicolas N Deeks Steven G SG Hecht Frederick M FM Palmer Sarah S

AIDS (London, England) 20200401 5

<h4>Objective</h4>The contribution of HLA-DR+ memory CD4 T cells to the HIV reservoir during prolonged antiretroviral therapy is unclear as these cells are commonly excluded when assessing for replication-competent HIV. To address this issue, we examined the distribution of genetically intact HIV DNA within HLA-DR- and HLA-DR+ memory CD4 T cells and the RNA transcriptional profile of these cells during antiretroviral therapy.<h4>Design/methods</h4>Full-length DNA sequencing was used to examine t ...[more]

PMID: 31913161

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Dataset Information

High levels of genetically intact HIV in HLA-DR+ memory T cells indicates their value for reservoir studies.

Objective

Design/methods

Results

Conclusion

Publications

High levels of genetically intact HIV in HLA-DR+ memory T cells indicates their value for reservoir studies.

Similar Datasets

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