CD32 is expressed on cells with transcriptionally active HIV but does not enrich for HIV DNA in resting T cells

Mohamed Abdel-Mohsen, Leticia Kuri-Cervantes, Judith Grau-Exposito, Adam M. Spivak, Racheal A. Nell, Costin Tomescu, Surya Kumari Vadrevu, Leila B. Giron, Carla Serra-Peinado, Meritxell Genescà, Josep Castellví, Guoxin Wu, Perla M. Del Rio Estrada, Mauricio González-Navarro, Kenneth Lynn, Colin T. King, Sai Vemula, Kara Cox, Yanmin Wan, Qingsheng LiKaram Mounzer, Jay Kostman, Ian Frank, Mirko Paiardini, Daria Hazuda, Gustavo Reyes-Terán, Douglas Richman, Bonnie Howell, Pablo Tebas, Javier Martinez-Picado, Vicente Planelles, Maria J. Buzon, Michael R. Betts, Luis J. Montaner

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numberY
JournalScience translational medicine
Volume10
Issue number437
DOIs
StatePublished - Apr 18 2018

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HIV
T-Lymphocytes
DNA
Lymphoid Tissue
RNA
HIV Infections
HLA-DR Antigens
Cell- and Tissue-Based Therapy
Fluorescence In Situ Hybridization
Blood Cells
Therapeutics
Lymph Nodes
Phenotype

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Abdel-Mohsen, M., Kuri-Cervantes, L., Grau-Exposito, J., Spivak, A. M., Nell, R. A., Tomescu, C., ... Montaner, L. J. (2018). CD32 is expressed on cells with transcriptionally active HIV but does not enrich for HIV DNA in resting T cells. Science translational medicine, 10(437), [Y]. https://doi.org/10.1126/scitranslmed.aar6759

CD32 is expressed on cells with transcriptionally active HIV but does not enrich for HIV DNA in resting T cells. / Abdel-Mohsen, Mohamed; Kuri-Cervantes, Leticia; Grau-Exposito, Judith; Spivak, Adam M.; Nell, Racheal A.; Tomescu, Costin; Vadrevu, Surya Kumari; Giron, Leila B.; Serra-Peinado, Carla; Genescà, Meritxell; Castellví, Josep; Wu, Guoxin; Del Rio Estrada, Perla M.; González-Navarro, Mauricio; Lynn, Kenneth; King, Colin T.; Vemula, Sai; Cox, Kara; Wan, Yanmin; Li, Qingsheng; Mounzer, Karam; Kostman, Jay; Frank, Ian; Paiardini, Mirko; Hazuda, Daria; Reyes-Terán, Gustavo; Richman, Douglas; Howell, Bonnie; Tebas, Pablo; Martinez-Picado, Javier; Planelles, Vicente; Buzon, Maria J.; Betts, Michael R.; Montaner, Luis J.

In: Science translational medicine, Vol. 10, No. 437, Y, 18.04.2018.

Research output: Contribution to journalArticle

Abdel-Mohsen, M, Kuri-Cervantes, L, Grau-Exposito, J, Spivak, AM, Nell, RA, Tomescu, C, Vadrevu, SK, Giron, LB, Serra-Peinado, C, Genescà, M, Castellví, J, Wu, G, Del Rio Estrada, PM, González-Navarro, M, Lynn, K, King, CT, Vemula, S, Cox, K, Wan, Y, Li, Q, Mounzer, K, Kostman, J, Frank, I, Paiardini, M, Hazuda, D, Reyes-Terán, G, Richman, D, Howell, B, Tebas, P, Martinez-Picado, J, Planelles, V, Buzon, MJ, Betts, MR & Montaner, LJ 2018, 'CD32 is expressed on cells with transcriptionally active HIV but does not enrich for HIV DNA in resting T cells', Science translational medicine, vol. 10, no. 437, Y. https://doi.org/10.1126/scitranslmed.aar6759
Abdel-Mohsen, Mohamed ; Kuri-Cervantes, Leticia ; Grau-Exposito, Judith ; Spivak, Adam M. ; Nell, Racheal A. ; Tomescu, Costin ; Vadrevu, Surya Kumari ; Giron, Leila B. ; Serra-Peinado, Carla ; Genescà, Meritxell ; Castellví, Josep ; Wu, Guoxin ; Del Rio Estrada, Perla M. ; González-Navarro, Mauricio ; Lynn, Kenneth ; King, Colin T. ; Vemula, Sai ; Cox, Kara ; Wan, Yanmin ; Li, Qingsheng ; Mounzer, Karam ; Kostman, Jay ; Frank, Ian ; Paiardini, Mirko ; Hazuda, Daria ; Reyes-Terán, Gustavo ; Richman, Douglas ; Howell, Bonnie ; Tebas, Pablo ; Martinez-Picado, Javier ; Planelles, Vicente ; Buzon, Maria J. ; Betts, Michael R. ; Montaner, Luis J. / CD32 is expressed on cells with transcriptionally active HIV but does not enrich for HIV DNA in resting T cells. In: Science translational medicine. 2018 ; Vol. 10, No. 437.
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abstract = "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.",
author = "Mohamed Abdel-Mohsen and Leticia Kuri-Cervantes and Judith Grau-Exposito and Spivak, {Adam M.} and Nell, {Racheal A.} and Costin Tomescu and Vadrevu, {Surya Kumari} and Giron, {Leila B.} and Carla Serra-Peinado and Meritxell Genesc{\`a} and Josep Castellv{\'i} and Guoxin Wu and {Del Rio Estrada}, {Perla M.} and Mauricio Gonz{\'a}lez-Navarro and Kenneth Lynn and King, {Colin T.} and Sai Vemula and Kara Cox and Yanmin Wan and Qingsheng Li and Karam Mounzer and Jay Kostman and Ian Frank and Mirko Paiardini and Daria Hazuda and Gustavo Reyes-Ter{\'a}n and Douglas Richman and Bonnie Howell and Pablo Tebas and Javier Martinez-Picado and Vicente Planelles and Buzon, {Maria J.} and Betts, {Michael R.} and Montaner, {Luis J.}",
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T1 - CD32 is expressed on cells with transcriptionally active HIV but does not enrich for HIV DNA in resting T cells

AU - Abdel-Mohsen, Mohamed

AU - Kuri-Cervantes, Leticia

AU - Grau-Exposito, Judith

AU - Spivak, Adam M.

AU - Nell, Racheal A.

AU - Tomescu, Costin

AU - Vadrevu, Surya Kumari

AU - Giron, Leila B.

AU - Serra-Peinado, Carla

AU - Genescà, Meritxell

AU - Castellví, Josep

AU - Wu, Guoxin

AU - Del Rio Estrada, Perla M.

AU - González-Navarro, Mauricio

AU - Lynn, Kenneth

AU - King, Colin T.

AU - Vemula, Sai

AU - Cox, Kara

AU - Wan, Yanmin

AU - Li, Qingsheng

AU - Mounzer, Karam

AU - Kostman, Jay

AU - Frank, Ian

AU - Paiardini, Mirko

AU - Hazuda, Daria

AU - Reyes-Terán, Gustavo

AU - Richman, Douglas

AU - Howell, Bonnie

AU - Tebas, Pablo

AU - Martinez-Picado, Javier

AU - Planelles, Vicente

AU - Buzon, Maria J.

AU - Betts, Michael R.

AU - Montaner, Luis J.

PY - 2018/4/18

Y1 - 2018/4/18

N2 - 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.

AB - 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.

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