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Type I interferons (IFNs) are essential for limiting HIV-2 progression. However, it is unclear whether and how Mtb affects HIV-2 coinfection by regulating type I IFNs. Here Mtb PE_PGRS62 protein was identified as an inhibitor of stimulator of interferon genes (STING)\u2013mediated type I IFN expression. Ectopic expression of PE_PGRS62 impaired type I IFN expression stimulated by cytosolic DNA, while knockout of pe_pgrs62 potentiated Mtb-induced type I IFN expression. PE_PGRS62 interacts directly with IFN regulatory factor (IRF) 3 and inhibits the interaction of IRF3 with TANK-binding kinase 1 (TBK1) as well as the binding of IRF3 to the IFN\u03b2 promoter. Furthermore, reduced HIV viral load was observed in pe_pgrs62 knockout Mtb-infected macrophages compared with wild-type Mtb. These findings reveal an important mechanism by which Mtb infection promotes HIV-2 immune evasion.<\/jats:p>","DOI":"10.1093\/infdis\/jiaf484","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T11:37:19Z","timestamp":1758022639000},"page":"e962-e971","source":"Crossref","is-referenced-by-count":0,"title":["<i>Mycobacterium tuberculosis<\/i>\n                    PE_PGRS62 Protein Inhibits Type I Interferon Responses to Promote HIV-2 Replication by Directly Interacting With Interferon Regulatory Factor 3"],"prefix":"10.1093","volume":"232","author":[{"given":"Chaohu","family":"Pan","sequence":"first","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology , Shenzhen, Guangdong ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Xu","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology , Shenzhen, Guangdong ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Huang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology , Shenzhen, Guangdong ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junyan","family":"He","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology , Shenzhen, Guangdong ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siqi","family":"Li","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology , Shenzhen, Guangdong ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyu","family":"Tao","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology , Shenzhen, Guangdong ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingzhi","family":"Cao","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology , Shenzhen, Guangdong ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3617-5449","authenticated-orcid":false,"given":"Guoliang","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology , Shenzhen, Guangdong ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,9,17]]},"reference":[{"key":"2026031304480476800_jiaf484-B1","doi-asserted-by":"crossref","first-page":"5905","DOI":"10.3390\/ijms24065905","article-title":"Antiretroviral treatment of HIV-2 infection: available drugs, resistance pathways, and promising new compounds","volume":"24","author":"Moranguinho","year":"2023","journal-title":"Int J Mol Sci"},{"key":"2026031304480476800_jiaf484-B2","doi-asserted-by":"crossref","first-page":"a017871","DOI":"10.1101\/cshperspect.a017871","article-title":"Tuberculosis and HIV coinfection","volume":"5","author":"Bruchfeld","year":"2015","journal-title":"Cold Spring Harb Perspect 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