Data for: Vaca et al., HIV proviral transcription and infectivity is enhanced by neddylation

Abstract (English)

Abstract: A spreading infection can quickly restart from the persistent reservoir of cells harboring HIV proviruses if antiretroviral therapy (ART) is stopped. HIV transcription can also be increased by latency reversing agents (LRAs) during ART. Neddylation is a post-translational modification that activates Cullin-RING ligases (CRLs) which ubiquitinate several proteins that regulate HIV transcription and infectivity, marking these regulators for proteasomal degradation. We studied how inhibiting neddylation affects HIV gene expression ex vivo after three LRAs: TNF𝛼, PMA and ionomycin, or JQ1. In provirus-containing T cells, broad inhibition of CRL-mediated ubiquitination using MLN4924 (MLN) with the above LRAs reduced HIV transcriptional initiation, decreased virus production, and diminished virion infectivity. Decreased degradation of an inhibitor of kB alpha (IkB𝛼) was implicated in reducing LRA-stimulated HIV transcription. MLN also decreased HIV reactivation after PMA and ionomycin treatment of CD4+ T cells from ART-suppressed people living with HIV. Results indicate that neddylation can enhance HIV proviral transcription and reactivated virion infectivity.

Importance: Results indicate that neddylation contributes to reactivating HIV provirus transcription and antigen expression, as well as enhancing infectivity of resulting virions, after three LRAs. This may inform new strategies for future research on ART-free remission of HIV infection. For example, future research inhibiting neddylation when ART stops may reduce provirus reactivation, while also limiting virus spread and establishment of new reservoir cells off-ART.