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Here, we used the U1 cell line to explore how SARS\u2010CoV\u20102 infection affects HIV\u20101 reactivation from latency, employing real\u2010time PCR assays and Western blot analysis. Our results show higher levels of HIV\u20101 RNA after SARS\u2010CoV\u20102 infection. Importantly, we noticed enhanced reactivation of HIV\u20101 replication in cells infected with viruses carrying a deletion of amino acids R<jats:sub>682<\/jats:sub>, R<jats:sub>683<\/jats:sub>, A<jats:sub>684<\/jats:sub> (RRA\u0394) in the spike (S) protein, compared to infections with viruses carrying the wild\u2010type S protein. This is involvement of host transcription factors like NFAT, NF\u2010\u03baB p65, Ap\u20101, and Sp\u20101, which facilitate HIV production via TCR\u2010related pathways. Additionally, activation of p\u2010TEFb pathways enhances transcription elongation, upregulates Jak\/Stat pathways, leading to increased viral replication, while TLR pathways impact the host immune response. Furthermore, RRA\u0394 showed increased apoptotic activity through both extrinsic and intrinsic apoptotic signaling pathways compared to wild\u2010type SARS\u2010CoV\u20102. These indicate that SARS\u2010CoV\u20102 infection could revive HIV\u20101 replication from latency. The deletion of amino acids R<jats:sub>682<\/jats:sub>R<jats:sub>683<\/jats:sub>A<jats:sub>684<\/jats:sub> in the viral S protein might regulate further HIV\u20101 replication and apoptotic conditions, potentially benefiting HIV\u20101 survival.<\/jats:p>","DOI":"10.1002\/jcp.70049","type":"journal-article","created":{"date-parts":[[2025,5,11]],"date-time":"2025-05-11T12:40:26Z","timestamp":1746967226000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["SARS\u2010CoV\u20102 Infection Reactivates HIV\u20101 Replication From Latency in U1 Cells"],"prefix":"10.1002","volume":"240","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6010-0121","authenticated-orcid":false,"given":"Xue","family":"Wang","sequence":"first","affiliation":[{"name":"Division of Emerging and Transfusion Transmitted Diseases Food and Drug Administration Silver Spring Maryland 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