CD32 + and PD-1 + Lymph Node CD4 T Cells Support Persistent HIV-1 Transcription in Treated Aviremic Individuals

• Published in: Journal of virology Vol. 92; no. 20
• Main Authors: Noto, Alessandra, Procopio, Francesco A., Banga, Riddhima, Suffiotti, Madeleine, Corpataux, Jean-Marc, Cavassini, Matthias, Riva, Agostino, Fenwick, Craig, Gottardo, Raphael, Perreau, Matthieu, Pantaleo, Giuseppe
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 15.10.2018
• Subjects: Adult; Anti-Retroviral Agents - therapeutic use; CD4-Positive T-Lymphocytes - chemistry; CD4-Positive T-Lymphocytes - virology; DNA, Viral - analysis; Female; HIV Infections - drug therapy; HIV Infections - pathology; HIV-1 - growth & development; Humans; Lymph Nodes - pathology; Male; Middle Aged; Pathogenesis and Immunity; Programmed Cell Death 1 Receptor - analysis; Receptors, IgG - analysis; RNA, Viral - analysis; T-Lymphocyte Subsets - chemistry; T-Lymphocyte Subsets - virology; Transcription, Genetic; Young Adult; human immunodeficiency virus; Tfh cells; PD-1; lymph node; CD32
• ISSN: 0022-538X; 1098-5514; 1098-5514
• DOI: 10.1128/JVI.00901-18

The existence of long-lived latently infected resting memory CD4 T cells represents a major obstacle to the eradication of HIV infection. Identifying cell markers defining latently infected cells containing replication-competent virus is important in order to determine the mechanisms of HIV persistence and to develop novel therapeutic strategies to cure HIV infection. We provide evidence that PD-1 and CD32 may have a complementary role in better defining CD4 T cell populations infected with HIV-1. Furthermore, CD4 T cells coexpressing CD32 and PD-1 identify a CD4 T cell population with high levels of persistent HIV-1 transcription. A recent study conducted in blood has proposed CD32 as the marker identifying the “elusive” HIV reservoir. We have investigated the distribution of CD32 + CD4 T cells in blood and lymph nodes (LNs) of HIV-1-uninfected subjects and viremic untreated and long-term-treated HIV-1-infected individuals and their relationship with PD-1 + CD4 T cells. The frequency of CD32 + CD4 T cells was increased in viremic compared to treated individuals in LNs, and a large proportion (up to 50%) of CD32 + cells coexpressed PD-1 and were enriched within T follicular helper (Tfh) cells. We next investigated the role of LN CD32 + CD4 T cells in the HIV reservoir. Total HIV DNA was enriched in CD32 + and PD-1 + CD4 T cells compared to CD32 − and PD-1 − cells in both viremic and treated individuals, but there was no difference between CD32 + and PD-1 + cells. There was no enrichment of latently infected cells with inducible HIV-1 in CD32 + versus PD-1 + cells in antiretroviral therapy (ART)-treated individuals. HIV-1 transcription was then analyzed in LN memory CD4 T cell populations sorted on the basis of CD32 and PD-1 expression. CD32 + PD-1 + CD4 T cells were significantly enriched in cell-associated HIV RNA compared to CD32 − PD-1 − (averages of 5.2-fold in treated individuals and 86.6-fold in viremics), CD32 + PD-1 − (2.2-fold in treated individuals and 4.3-fold in viremics), and CD32 − PD-1 + (2.2-fold in ART-treated individuals and 4.6-fold in viremics) cell populations. Similar levels of HIV-1 transcription were found in CD32 + PD-1 − and CD32 − PD-1 + CD4 T cells. Interestingly, the proportion of CD32 + and PD-1 + CD4 T cells negatively correlated with CD4 T cell counts and length of therapy. Therefore, the expression of CD32 identifies, independently of PD-1, a CD4 T cell population with persistent HIV-1 transcription and coexpression of CD32 and PD-1, the CD4 T cell population with the highest levels of HIV-1 transcription in both viremic and treated individuals. IMPORTANCE The existence of long-lived latently infected resting memory CD4 T cells represents a major obstacle to the eradication of HIV infection. Identifying cell markers defining latently infected cells containing replication-competent virus is important in order to determine the mechanisms of HIV persistence and to develop novel therapeutic strategies to cure HIV infection. We provide evidence that PD-1 and CD32 may have a complementary role in better defining CD4 T cell populations infected with HIV-1. Furthermore, CD4 T cells coexpressing CD32 and PD-1 identify a CD4 T cell population with high levels of persistent HIV-1 transcription.