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.