Evidence that CD32a does not mark the HIV-1 latent reservoir

Osuna, Christa E.; Lim, So-Yon; Kublin, Jessica; Apps, Richard; Chen, Elsa; Mota, Talia M.; Huang, Szu-Han; Ren, Yanqin; Bachtel, Nathaniel D.; Tsibris, Athe; Ackerman, Margaret E.; Jones, R. Brad; Nixon, Douglas F.; Whitney, James B.

doi:10.1038/s41586-018-0495-2

Cited by 45 publications

(55 citation statements)

References 15 publications

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“…Recently, the expression of CD32a has been reported as a potential marker of memory CD4 + T cells harboring a replication-competent latent virus in aviremic patients under ART (Descours et al, 2017;Darcis et al, 2019). The role of CD32a as a cellular marker of HIV-1 reservoirs has been the subject of several works Martin et al, 2018;Osuna et al, 2018;Thornhill et al, 2019). A complete study presented at CROI by Darcis et al (CROI 2019, Poster 346 -CD32 + CD4 + T cells are enriched in HIV-1 DNA) showed that active CD4 + T cells co-expressing HLA-DR and CD32a are highly enriched with HIV-1 DNA.…”

Section: Markers Of Latently-infected Cd4 + T Cellsmentioning

confidence: 99%

Current Status of Latency Reversing Agents Facing the Heterogeneity of HIV-1 Cellular and Tissue Reservoirs

Aït-Ammar

Kula

Darcis³

et al. 2020

Front. Microbiol.

128

150

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Quantitative polymerase chain reaction; QVOA, quantitative viral outgrowth assays; Rev, regulator of virion expression; RNA, ribonucleic acid; RNAPII, RNA polymerase II; RT-ddPCR, teverse transcription droplet digital PCR; SAHA, suberoylanilide hydroxamic acid; SIV, simian immunodeficiency virus; SMAC, second mitochondrial activator of caspases; SMYD2, SET (Suppressor of variegation, Enhancer of Zeste, Trithorax) and MYND (Myeloid-Nervy-DEAF1) domain-containing protein 2; Sp1, specificity protein 1; STAT5, signal transducer and activator of transcription 5; Suv39H1, Suppressor of variegation 3-9 homolog 1

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Section: Markers Of Latently-infected Cd4 + T Cellsmentioning

confidence: 99%

Current Status of Latency Reversing Agents Facing the Heterogeneity of HIV-1 Cellular and Tissue Reservoirs

Aït-Ammar

Kula

Darcis³

et al. 2020

Front. Microbiol.

128

150

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“…As we had previously shown that CD32 high CD4 T cells from PBMCs expressed non-T-cell lineage markers 18 and others have demonstrated these cells to be doublets, 17 we wanted to explore whether these singlet-gated events were also T-cell-B-cell doublets. We stained PBMCs from healthy donors for CD4 T (CD3 and CD4) and B-cell markers (CD19) as well as CD32 and acquired the samples using imaging flow cytometry, which allows the visualisation of the fluorescence distribution on individual cell events.…”

Section: Cd32 High Cells Are Primarily T-cell-b-cell Doubletsmentioning

confidence: 99%

“…Recent work suggesting that CD32a (a low-affinity IgG receptor not generally expressed on T cells 10 ) was a specific marker for latent HIV infection 11 was initially supported by studies showing that CD32 may be found on cells that are transcriptionally active, and was associated with HIV DNA levels in some patients. [12][13][14][15][16][17][18][19] However, the finding that CD32 co-expression with CD4 is predominantly due to T-cell-B-cell doublets 17 likely undermines the argument that CD32 is a definitive marker of latency.…”

Section: Introductionmentioning

confidence: 99%

CD32 expressing doublets in HIV-infected gut-associated lymphoid tissue are associated with a T follicular helper cell phenotype

et al. 2019

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Gut-associated lymphoid tissue (GALT) is a key location for the HIV reservoir. The observation that B-cell-T-cell doublets are enriched for CD32a (a low-affinity IgG receptor) in peripheral blood raises interesting questions, especially as these cells have been associated with HIV DNA in some studies. We sought to determine if similar doublets were present in GALT, the significance of these doublets, and their implications for the HIV reservoir. Given the importance of GALT as a reservoir for HIV, we looked for expression of CD32 on gut CD4 T cells and for evidence of doublets, and any relationship with HIV DNA in HIV + individuals initiated on antiretroviral therapy (ART) during primary HIV infection (PHI). Tonsil tissue was also available for one individual. As previously shown for blood, CD32 high CD4 cells were mainly doublets of CD4 T cells and B cells, with T-cell expression of ICOS in tonsil and gut tissue. CD4 T cells associated with CD32 (compared with 'CD32−' CD4 cells) had higher expression of follicular markers CXCR5, PD-1, ICOS, and Bcl-6 consistent with a T follicular helper (TFH) phenotype. There was a significant correlation between rectal HIV DNA levels and CD32 expression on TFH cells. Together, these data suggest that CD32 high doublets are primarily composed of TFH cells, a subset known to be preferentially infected by HIV.

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“…Recently, CD32+ CD4 T cells have been proposed to be a major host of the LR, whereby selection of this cell population resulted in significant enrichment of inducible provirus (Descours et al, 2017;Darcis et al, 2020). Conflicting reports, however, have failed to replicate this finding and the contribution of CD32+ CD4 T cells to HIV-1 persistence and rebound remains controversial (Abdel-Mohsen et al, 2018;Badia et al, 2018;Bertagnolli et al, 2018;Martin et al, 2018;Osuna et al, 2018;Pérez et al, 2018). Nonetheless, the use of CD32 as a marker of latent infection is a topic of particular interest and may provide a mechanism by which the LR can be specifically targeted.…”

Section: The Hosts Of the Reservoirmentioning

confidence: 99%

Measuring the Success of HIV-1 Cure Strategies

Thomas

Ruggiero

Paxton

et al. 2020

Front. Cell. Infect. Microbiol.

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HIV-1 eradication strategies aim to achieve viral remission in the absence of antiretroviral therapy (ART). The development of an HIV-1 cure remains challenging due to the latent reservoir (LR): long-lived CD4 T cells that harbor transcriptionally silent HIV-1 provirus. The LR is stable despite years of suppressive ART and is the source of rebound viremia following therapy interruption. Cure strategies such as "shock and kill" aim to eliminate or reduce the LR by reversing latency, exposing the infected cells to clearance via the immune response or the viral cytopathic effect. Alternative strategies include therapeutic vaccination, which aims to prime the immune response to facilitate control of the virus in the absence of ART. Despite promising advances, these strategies have been unable to significantly reduce the LR or increase the time to viral rebound but have provided invaluable insight in the field of HIV-1 eradication. The development and assessment of an HIV-1 cure requires robust assays that can measure the LR with sufficient sensitivity to detect changes that may occur following treatment. The viral outgrowth assay (VOA) is considered the gold standard method for LR quantification due to its ability to distinguish intact and defective provirus. However, the VOA is time consuming and resource intensive, therefore several alternative assays have been developed to bridge the gap between practicality and accuracy. Whilst a cure for HIV-1 infection remains elusive, recent advances in our understanding of the LR and methods for its eradication have offered renewed hope regarding achieving ART free viral remission.

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Evidence that CD32a does not mark the HIV-1 latent reservoir

Cited by 45 publications

References 15 publications

Current Status of Latency Reversing Agents Facing the Heterogeneity of HIV-1 Cellular and Tissue Reservoirs

Current Status of Latency Reversing Agents Facing the Heterogeneity of HIV-1 Cellular and Tissue Reservoirs

CD32 expressing doublets in HIV-infected gut-associated lymphoid tissue are associated with a T follicular helper cell phenotype

Measuring the Success of HIV-1 Cure Strategies

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