TY - JOUR
T1 - The latent human immunodeficiency virus (HIV) reservoir resides primarily in CD32 - CD4 + T Cells in Perinatally HIV-Infected Adolescents with Long-Term Virologic Suppression
AU - Dhummakupt, Adit
AU - Siems, Lilly V.
AU - Singh, Dolly
AU - Chen, Ya Hui
AU - Anderson, Thuy
AU - Collinson-Streng, Aleisha
AU - Zhang, Hao
AU - Patel, Purvish
AU - Agwu, Allison
AU - Persaud, Deborah
N1 - Publisher Copyright:
© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Background High-level expression of the Fc3 receptor, CD32 hi, on CD4 + T cells was associated with enhanced human immunodeficiency virus (HIV) infection of the latent reservoir in a study of adults receiving antiretroviral therapy. We tested the hypothesis that CD32 was the preferential marker of the latent HIV reservoir in virally suppressed, perinatally HIV-infected adolescents. Methods The frequency of CD32 hi CD4 + T cells was determined by flow cytometry (N = 5) and the inducible HIV reservoir in both CD32 hi and CD32 - CD4 + T cells was quantified (N = 4) with a quantitative viral outgrowth assay. Viral outgrowth was measured by the standard p24 enzyme-linked immunosorbent assay and an ultrasensitive p24 assay (Simoa; Quanterix) with lower limits of quantitation. Results We found a 59.55-fold enrichment in the absolute number of infectious cells in the CD32 - population compared with CD32 hi cells. Exponential HIV replication occurred exclusively in CD32 - CD4 + T cells (mean change, 17.46 pg/mL; P =.04). Induced provirus in CD32 hi CD4 + T cells replicated to substantially lower levels, which did not increase significantly over time (mean change, 0.026 pg/mL; P =.23) and were detected only with the Simoa assay. Conclusions Our data suggests that the latent HIV reservoir resides mainly in CD32 - CD4 + T cells in virally suppressed, perinatally HIV-infected adolescents, which has implications for reservoir elimination strategies.
AB - Background High-level expression of the Fc3 receptor, CD32 hi, on CD4 + T cells was associated with enhanced human immunodeficiency virus (HIV) infection of the latent reservoir in a study of adults receiving antiretroviral therapy. We tested the hypothesis that CD32 was the preferential marker of the latent HIV reservoir in virally suppressed, perinatally HIV-infected adolescents. Methods The frequency of CD32 hi CD4 + T cells was determined by flow cytometry (N = 5) and the inducible HIV reservoir in both CD32 hi and CD32 - CD4 + T cells was quantified (N = 4) with a quantitative viral outgrowth assay. Viral outgrowth was measured by the standard p24 enzyme-linked immunosorbent assay and an ultrasensitive p24 assay (Simoa; Quanterix) with lower limits of quantitation. Results We found a 59.55-fold enrichment in the absolute number of infectious cells in the CD32 - population compared with CD32 hi cells. Exponential HIV replication occurred exclusively in CD32 - CD4 + T cells (mean change, 17.46 pg/mL; P =.04). Induced provirus in CD32 hi CD4 + T cells replicated to substantially lower levels, which did not increase significantly over time (mean change, 0.026 pg/mL; P =.23) and were detected only with the Simoa assay. Conclusions Our data suggests that the latent HIV reservoir resides mainly in CD32 - CD4 + T cells in virally suppressed, perinatally HIV-infected adolescents, which has implications for reservoir elimination strategies.
KW - CD32 HIV reservoir
KW - HIV latent reservoir
KW - HIV/AIDS
KW - perinatal infection
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U2 - 10.1093/infdis/jiy461
DO - 10.1093/infdis/jiy461
M3 - Article
C2 - 30053296
AN - SCOPUS:85056361899
SN - 0022-1899
VL - 219
SP - 80
EP - 88
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 1
ER -