Involvement of lncRNA TUG1 in HIV-1 Tat-Induced Astrocyte Senescence

Prakash P. Pillai, Muthukumar Kannan, Susmita Sil, Seema Singh, Annadurai Thangaraj, Ernest T. Chivero, Raghubendra Singh Dagur, Ashutosh Tripathi, Guoku Hu, Palsamy Periyasamy, Shilpa Buch

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


HIV-1 infection in the era of combined antiretroviral therapy has been associated with premature aging. Among the various features of HIV-1 associated neurocognitive disorders, astrocyte senescence has been surmised as a potential cause contributing to HIV-1-induced brain aging and neurocognitive impairments. Recently, lncRNAs have also been implicated to play essential roles in the onset of cellular senescence. Herein, using human primary astrocytes (HPAs), we investigated the role of lncRNA TUG1 in HIV-1 Tat-mediated onset of astrocyte senescence. We found that HPAs exposed to HIV-1 Tat resulted in significant upregulation of lncRNA TUG1 expression that was accompanied by elevated expression of p16 and p21, respectively. Additionally, HIV-1 Tat-exposed HPAs demonstrated increased expression of senescence-associated (SA) markers—SA-β-galactosidase (SA-β-gal) activity and SA-heterochromatin foci—cell-cycle arrest, and increased production of reactive oxygen species and proinflammatory cytokines. Intriguingly, gene silencing of lncRNA TUG1 in HPAs also reversed HIV-1 Tat-induced upregulation of p21, p16, SA-β gal activity, cellular activation, and proinflammatory cytokines. Furthermore, increased expression of astrocytic p16 and p21, lncRNA TUG1, and proinflammatory cytokines were observed in the prefrontal cortices of HIV-1 transgenic rats, thereby suggesting the occurrence of senescence activation in vivo. Overall, our data indicate that HIV-1 Tat-induced astrocyte senescence involves the lncRNA TUG1 and could serve as a potential therapeutic target for dampening accelerated aging associated with HIV-1/HIV-1 proteins.

Original languageEnglish (US)
Article number4330
JournalInternational journal of molecular sciences
Issue number5
StatePublished - Mar 2023


  • HIV-1 Tat
  • aging
  • astrocyte senescence
  • lncRNA TUG1
  • proinflammatory cytokines

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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