SRA

While gut and lymph node (LN) memory CD4 T cells represent major HIV and SIV tissue reservoirs, 33 the study of the role of dendritic cells (DCs) in HIV persistence has long been limited to the blood due 34 to the difficulties to access lymphoid tissue samples. In the present study, we showed that LN migratory 35 and resident DCs subpopulations harbored distinct phenotypic and transcriptomic profiles. Interestingly, 36 both LN DC subpopulations contained HIV intact provirus and inducible replication competent HIV 37 despite the expression of the anti-viral restriction factor SAMHD1. Notably, LN DC subpopulations 38 isolated from HIV-infected individuals treated for up to 14 years are transcriptionally silent but harbored 39 replication competent virus that can be induced upon TLR7/8 agonist stimulation. Subsequent single 40 cell RNAseq and single genome HIV proviral sequencing with matched integration site analyses 41 revealed that persistence of HIV-infected DCs in vivo was associated with rare but detectable clonal 42 proliferation of DCs and the upregulation of BIRC3 anti-apoptotic molecule. Taken together, these 43 results uncovered a potential important contribution of LN DCs to the HIV reservoir and to the 44 mechanisms responsible for HIV persistence.