Inhibition of HIV-1 replication in viral mutants with altered TAR RNA stem structures

Virology
M P RounsevilleA Kumar

Abstract

Human immunodeficiency virus type 1 (HIV-1) Tat-mediated trans-activation requires the structural integrity of TAR RNA and the cooperative interaction of human host cell proteins. The TAR domain, minimally required for tat response, includes the Tat binding pyrimidine bulge, the TAR RNA upper stem, and the loop sequences. However, little is known about the significance of the 5'-stem structure of TAR in the regulation of viral growth. We designed viral mutations, specifically in the TAR RNA lower stem structure, and studied their effects on the kinetics of viral growth in T-lymphocyte cell lines and in activated human peripheral blood mononuclear cells. Mutations that destabilized the lower TAR stem structure inhibited viral growth to various degrees in different CD4+ T-cells. These results suggest that the structural integrity of the lower stem structure of TAR plays an important role in viral growth, presumably by binding to specific host cell proteins that stabilize Tat-TAR interactions.

Citations

Sep 27, 2001·Antisense & Nucleic Acid Drug Development·C MischiatiR Gambari
Jul 9, 1998·Journal of Biotechnology·A MarozziE Ginelli
Nov 16, 2004·The Journal of Biological Chemistry·Christian Lanciault, James J Champoux
Feb 21, 2021·European Journal of Medicinal Chemistry·Ramandeep Kaur, Kapil Kumar

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