RhCMV Expands CCR5 Memory T Cells and promotes SIV reservoir seeding in the Gut Mucosa

Cytomegalovirus (CMV) is a prevalent ß-herpesvirus that persists asymptomatically in immunocompetent hosts. In people with HIV-1 (PWH), CMV is associated with HIV-1 persistence and particular inflammatory-related co-morbidities. The true causative role of CMV in HIV-associated pathologies however remains unclear given that nearly all PWH are coinfected with CMV. In this study, we examined acute phase immune and virological dynamics in cohorts of SIV-infected rhesus macaques (RMs) that were naturally seropositive or -negative for rhesus CMV (RhCMV). We observed prior to SIV, RhCMV expanded a polyclonal population of target CCR5+CD4+ T cells in gut and lymph nodes (LN) that expressed the chemotactic receptor CXCR3 and were largely not specific for RhCMV. Upon SIV infection, RhCMV+ RMs exhibited higher peak viremia and elevated levels of SIV DNA in the upper and lower intestine. Greater seeding of SIV DNA was associated with a maintenance of CCR5-expressing CD4+ T cells that were enriched within the RhCMV+ gut along a CXCR3-CXCL9 chemotactic axis. Overall, the data suggest that RhCMV can promote SIV susceptibility within a diverse, polyclonal pool of CD4 T cells that are not entirely RhCMV-specific. Overall design: Bulk RNA TCR-seq was performed on sorted CD4+CCR5+ and CD4+CMV-specific T cells from 5 rhesus macaques. CMV-specific T cells were identified and sorted using an activation-induced marker assay following in vitro stimulation with CMV lysate.