HIV-1 replication in CD4+ T cells exploits the down-regulation of antiviral NEAT1 long non-coding RNAs following T cell activation

Abstract

The related NEAT1_1 and NEAT1_2 long noncoding RNAs (lnc RNAs) have been recently implicated in innate immunity against viral infection. We used CRISPR-Cas9 to generate Jurkat CD4⁺ T cell lines with a knockout (KO) of the NEAT1 gene. Viabilities of NEAT1 KO Jurkat lines were indistinguishable from parental Jurkat cells, as was the induction of CD69 after T cell activation. The KO lines were however more sensitive to the induction of apoptosis than parental Jurkat cells. HIV-1 replication was higher in the KO lines than parental Jurkat cells, demonstrating an anti-HIV function of NEAT1 lncRNAs. We observed a strong down-regulation of NEAT1 lncRNAs following activation of resting peripheral blood mononuclear cells and purified CD4⁺ T cells. These findings indicate that HIV-1 infection exploits the normal down-regulation of anti-viral NEAT1 lncRNAs in activated CD4⁺ T cells to enhance viral replication.

Keywords: HIV; Long non-coding RNA; NEAT1 lncRNA; Viral replication.