Nuclear translocation of triosephosphate isomerase 1 under aerobic glycolytic conditions is associated with HIV-1 transcription.

The metabolic state of HIV-1-infected cells influences viral gene expression, with aerobic glycolytic conditions favoring HIV-1 transcription. Here, we demonstrate that under aerobic glycolytic conditions in HIV-1-infected cells, triosephosphate isomerase 1 (TPI1) undergoes nuclear translocation and promotes HIV-1 transcription. HIV-1-infected cells cultured in glucose-containing medium, which promotes aerobic glycolytic conditions, exhibited significantly higher levels of HIV-1 transcription than those cultured in galactose-containing medium, which favors oxidative phosphorylation. Under glucose conditions, TPI1 displayed a characteristic acidic isoform in HIV-1-infected cells. Overexpression of TPI1 increased this acidic isoform and enhanced HIV-1 transcription, whereas the S80A mutant failed to do so. These findings indicate that Ser80 plays a critical role in TPI1 nuclear localization and HIV-1 transcription. Consistently, nuclear TPI1 levels were markedly reduced under galactose conditions, in S80A-expressing cells, or upon TPI1 knockdown. Reduced nuclear TPI1 levels were associated with decreased H3K27 acetylation and diminished HIV-1 transcriptional activity. Moreover, TPI1 localization was unaffected by metabolic conditions in uninfected PBMCs but showed nuclear translocation under aerobic glycolytic conditions in HIV-1-infected PBMCs. Collectively, these findings suggest that, in HIV-1-infected cells, aerobic glycolytic conditions promote TPI1 nuclear translocation, thereby linking cellular metabolism to HIV-1 transcription.