Anatomical, subset, and HIV-dependent expression of viral sensors and restriction factors

The fate of a cell exposed to HIV is affected by its ability to sense the virus and restrict its replication. To explore this, we developed VIral SensOr Restriction factor-CyTOF (VISOR-CyTOF), which profiles 19 viral sensors and restriction factors (VISORs) simultaneously in single cells, and applied it to 41 post-mortem tissues from people with HIV. We found that myeloid cells, particularly those in mucosa, are well-equipped with SAMHD1 and sensors of viral capsid and DNA, while CD4+ T cells – particularly the highly-susceptible Tem subset – are not. In lymph node CD4+ Tfh, VISOR expression patterns favor HIV integration while blocking HIV gene expression, thus favoring viral latency. HIV preferentially fuses to CD4+ T cells with a permissive VISOR profile, but early induction of select VISORs by type I interferon prevents productive HIV infection. Our findings document the diverse patterns of VISOR profiles across tissues and cell subsets, and define their association with susceptibility to HIV.