| Title: |
HIV-1 infection regulates gene expression by altering alternative polyadenylation correlated with CPSF6 and CPSF5 redistribution |
| Authors: |
Charlotte Luchsinger; Annie Zhi Dai; Hari Yalamanchili; Aiswarya Balakrishnan; Kai-Lieh Huang; Cinzia Bertelli; Bin Cui; Ramon Lorenzo-Redondo; Eric J. Wagner; Felipe Diaz-Griffero |
| Source: |
mBio, Vol 17, Iss 1 (2026) |
| Publisher Information: |
American Society for Microbiology |
| Publication Year: |
2026 |
| Collection: |
Directory of Open Access Journals: DOAJ Articles |
| Subject Terms: |
HIV-1; CPSF6; CPSF5; capsid; alternative polyadenylation(APA); gene expression; Microbiology; QR1-502 |
| Description: |
HIV-1 viral core transport to the nucleus, an early infection event, triggers the redistribution of cleavage and polyadenylation specificity factors (CPSF) 5 and CPSF6 to nuclear speckles, forming puncta-like structures. CPSF5 and CPSF6 regulate alternative polyadenylation (APA), which governs approximately 70% of gene expression. APA alters the lengths of mRNA 3’-untranslated regions (3′-UTRs), which contain regulatory signals influencing RNA stability, localization, and function. We investigated whether HIV-1 infection–induced changes in CPSF5 and CPSF6 subcellular localization are accompanied by APA changes. Using two independent methodologies to assess APA in human cell lines and primary CD4+ T cells, we found that HIV-1 infection regulates APA, shaped by the interaction of CPSF6 with the viral capsid, recapitulating the APA phenotype observed in CPSF6 knockout cells. Our study demonstrates that HIV-1 infection leverages the interaction between the viral capsid and CPSF6 to co-opt cellular processes, alter gene expression, and potentially contribute to viral pathogenesis.IMPORTANCEThe interaction between HIV-1 and the cellular protein CPSF6 has been known for over 15 years; however, depletion of CPSF6 does not impair productive infection. An alternative possibility is that the virus exploits this protein to modulate cellular processes. This study demonstrates that HIV-1 infection alters the cellular function of CPSF6, an essential regulator of alternative polyadenylation—a mechanism that controls 70% of gene expression. Here, we show that HIV-1 regulates gene expression by disrupting the alternative polyadenylation function of CPSF6 through direct interaction. Overall, this reveals a novel strategy employed by the virus to modulate cellular gene expression. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://doaj.org/toc/2150-7511; https://doaj.org/article/2d2d137ae6464837bdd3984b6a5b2951 |
| DOI: |
10.1128/mbio.02865-25 |
| Availability: |
https://doi.org/10.1128/mbio.02865-25; https://doaj.org/article/2d2d137ae6464837bdd3984b6a5b2951 |
| Accession Number: |
edsbas.83D733D |
| Database: |
BASE |