Importance of the second exon of HIV-1 Tat on the survival of neuronal progenitors

• Published in: Journal of neurovirology 2007-01, Vol.13, p.111-111
• Main Authors: Passiatore, G, Gualco, E, Reiss, K, Eletto, D, Khalili, K, Peruzzi, F
• Format: Article
• Language: English
• Subjects: Human immunodeficiency virus 1
• ISSN: 1355-0284

HIV-Encephalopathy (HIVE) is a neurological disorder associated with HIV-1 infection and AIDS. Among the molecular mechanisms thought to participate in neuronal dysfunction, the viral trans-activating protein Tat has been shown to be neurotoxic in various cellular models. Tat gene consists of two exons that encode for two variants of the protein, which are 72 and 101 amino acids in length, respectively. Although the 101 aa Tat is considered the natural full-length isoform of Tat, shorter peptides of 72 and 86 amino acids are often used for in vitro experiments. While it is clear that the first exon (72 aa in length) is required for viral replication, the function of the carboxy-terminal region of Tat is less clear. Here, we utilized a rat neuronal progenitor cell line as a model of retinoic acid induced neuronal differentiation and various plasmids for the expression of C-terminus truncated mutants of Tat protein: Tat-72, Tat-86, and Tat-101. Our results strongly suggest that: (i) truncation of the C-terminus correlates with higher toxicity in both proliferating and differentiating cells; and (ii) survival of Tat-transfected cells is enhanced upon retinoic acid treatment and induction of cellular differentiation. Altogether, these results indicate that neuronal toxicity of Tat is attenuated by the presence of a sequence in the second exon and by the activation of neuronal differentiation.