Anatomical, subset, and HIV-dependent expression of viral sensors and restriction factors
We developed viral sensor and restriction factor-cytometry by time of flight (VISOR-CyTOF), which profiles 19 viral sensors and restriction factors (VISORs) simultaneously in single cells, and applied it to 41 postmortem tissues from people with HIV. Mucosal myeloid cells are well equipped with SAMHD1 and sensors of viral capsid and DNA while CD4<sup>+</sup> T cells are not. In lymph node CD4<sup>+</sup> Tfh, VISOR expression patterns reflect those favoring integration but blocking HIV gene expression, thus favoring viral latency. We also identify small subsets of bone marrow-, lung-, and gut-associated CD4<sup>+</sup> T and myeloid cells expressing high levels of restriction factors targeting most stages of the HIV replication cycle. In vitro, HIV preferentially fuses to CD4<sup>+</sup> T cells with a permissive VISOR profile, but early induction of select VISORs by T1IFN prevents productive HIV infection. Our findings document the diverse patterns of VISOR profiles across tissues and cellular subsets and define their association with susceptibility to HIV.
Authors
- Alicer K. Andrew (ORCID: https://orcid.org/0000-0003-4909-0759)
- Ashley F. George (ORCID: https://orcid.org/0000-0002-1482-5244)
- Antoine Chaillon (ORCID: https://orcid.org/0000-0001-9490-3857)
- Julie Frouard (ORCID: https://orcid.org/0000-0002-6296-2534)
- Reuben Thomas (ORCID: https://orcid.org/0000-0003-3176-7303)
- Brendon Woodworth (ORCID: https://orcid.org/0000-0003-3412-0396)
- Magali Porrachia
- Davey M. Smith (ORCID: https://orcid.org/0000-0003-3603-1733)
- Ifeanyi Jude Ezeonwumelu (ORCID: https://orcid.org/0000-0003-4007-2212)
- Jason Neidleman (ORCID: https://orcid.org/0000-0003-3525-8047)
- Kyrlia C. Young
- Martin R. Jakobsen (ORCID: https://orcid.org/0000-0001-8847-9201)
- Natalie Elphick (ORCID: https://orcid.org/0009-0006-3941-1095)
- Sara Gianella (ORCID: https://orcid.org/0000-0002-9927-0849)
- Xiaoyu Luo (ORCID: https://orcid.org/0000-0001-6059-0434)
- Kailin Yin (ORCID: https://orcid.org/0000-0002-9827-7774)
- Tongcui Ma
- Nadia R. Roan (ORCID: https://orcid.org/0000-0002-5464-1976)
- Jesper G Pedersen
Institutions
- Gladstone Institutes (US)
- Aarhus University (DK)
- University of California San Diego (US)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-01-01
- DOI
- https://doi.org/10.1016/j.celrep.2024.115202
- Citations
- 3
- Primary Topic
- interferon and immune responses
- Type
- article
- Field-Weighted Citation Impact
- 2.39
Funders
- Gilead Sciences
- James B. Pendleton Charitable Trust
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Child Health and Human Development
- Alcon Research Institute