Nef-induced differential gene expression in primary CD4+ T cells following infection with HIV-1 isolates

Almost 80% of viral transcripts during early HIV-1 infection encode the Nef protein, which has been implicated in altering expression of a number of genes. In this study, we infected primary human CD4⁺ T cells with pseudotyped Nef-containing or Nef-deleted (Δ-nef) NL4-3 virus and used RNA-Sequencing (RNA-Seq) for transcriptomic analysis. Our results showed that the interferon response, IL-15 and JAK/STAT signaling, as well as genes involved in metabolism, apoptosis, cell cycle regulation, and ribosome biogenesis were all altered in the presence of Nef. These early Nef-mediated transcriptional alterations may play a role in priming the host cell for cellular activation and viral replication.