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CD32 is expressed on cells with transcriptionally active HIV but does not enrich for HIV DNA in resting T cells
Science Translational Medicine ( IF 17.1 ) Pub Date : 2018-04-18 , DOI: 10.1126/scitranslmed.aar6759
Mohamed Abdel-Mohsen 1 , Leticia Kuri-Cervantes 2 , Judith Grau-Exposito 3 , Adam M Spivak 4 , Racheal A Nell 4 , Costin Tomescu 1 , Surya Kumari Vadrevu 1 , Leila B Giron 1 , Carla Serra-Peinado 3 , Meritxell Genescà 3 , Josep Castellví 5 , Guoxin Wu 6 , Perla M Del Rio Estrada 7 , Mauricio González-Navarro 7 , Kenneth Lynn 1, 2, 8 , Colin T King 9 , Sai Vemula 6 , Kara Cox 6 , Yanmin Wan 10 , Qingsheng Li 10 , Karam Mounzer 8 , Jay Kostman 8 , Ian Frank 2 , Mirko Paiardini 9 , Daria Hazuda 6 , Gustavo Reyes-Terán 7 , Douglas Richman 11 , Bonnie Howell 6 , Pablo Tebas 2 , Javier Martinez-Picado 12, 13, 14 , Vicente Planelles 4 , Maria J Buzon 3 , Michael R Betts 2 , Luis J Montaner 1
Affiliation  

The persistence of HIV reservoirs, including latently infected, resting CD4+ T cells, is the major obstacle to cure HIV infection. CD32a expression was recently reported to mark CD4+ T cells harboring a replication-competent HIV reservoir during antiretroviral therapy (ART) suppression. We aimed to determine whether CD32 expression marks HIV latently or transcriptionally active infected CD4+ T cells. Using peripheral blood and lymphoid tissue of ART-treated HIV+ or SIV+ subjects, we found that most of the circulating memory CD32+ CD4+ T cells expressed markers of activation, including CD69, HLA-DR, CD25, CD38, and Ki67, and bore a TH2 phenotype as defined by CXCR3, CCR4, and CCR6. CD32 expression did not selectively enrich for HIV- or SIV-infected CD4+ T cells in peripheral blood or lymphoid tissue; isolated CD32+ resting CD4+ T cells accounted for less than 3% of the total HIV DNA in CD4+ T cells. Cell-associated HIV DNA and RNA loads in CD4+ T cells positively correlated with the frequency of CD32+ CD69+ CD4+ T cells but not with CD32 expression on resting CD4+ T cells. Using RNA fluorescence in situ hybridization, CD32 coexpression with HIV RNA or p24 was detected after in vitro HIV infection (peripheral blood mononuclear cell and tissue) and in vivo within lymph node tissue from HIV-infected individuals. Together, these results indicate that CD32 is not a marker of resting CD4+ T cells or of enriched HIV DNA–positive cells after ART; rather, CD32 is predominately expressed on a subset of activated CD4+ T cells enriched for transcriptionally active HIV after long-term ART.



中文翻译:

CD32 在具有转录活性 HIV 的细胞上表达,但在静息 T 细胞中不富集 HIV DNA

HIV 储存库的持续存在,包括潜伏感染的静息 CD4 + T 细胞,是治愈 HIV 感染的主要障碍。最近有报道称,在抗逆转录病毒治疗 (ART) 抑制期间,CD32a 表达可标记具有复制能力的 HIV 病毒库的 CD4 + T 细胞。我们的目的是确定 CD32 表达是否标记 HIV 潜伏或转录活性感染的 CD4 + T 细胞。使用接受 ART 治疗的 HIV +或 SIV +受试者的外周血和淋巴组织,我们发现大多数循环记忆 CD32 + CD4 + T 细胞表达激活标记物,包括 CD69、HLA-DR、CD25、CD38 和 Ki67,并具有由 CXCR3、CCR4 和 CCR6 定义的T H 2 表型。CD32 表达并未选择性富集外周血或淋巴组织中HIV 或 SIV 感染的 CD4 + T 细胞;分离的CD32 +静息CD4 + T细胞占CD4 + T细胞中HIV DNA总量的不到3% 。CD4 + T 细胞中细胞相关的 HIV DNA 和 RNA 负载与 CD32 + CD69 + CD4 + T 细胞的频率呈正相关,但与静息 CD4 + T 细胞上的 CD32 表达不相关。使用 RNA 荧光原位杂交,在体外 HIV 感染(外周血单核细胞和组织)后以及体内 HIV 感染者的淋巴结组织内检测到 CD32 与 HIV RNA 或 p24 的共表达。总之,这些结果表明 CD32 不是 ART 后静息 CD4 + T 细胞或富集的 HIV DNA 阳性细胞的标记;相反,CD32 主要在长期 ART 后富含转录活性 HIV 的活化 CD4 + T 细胞亚群上表达。

更新日期:2018-04-19
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