QIMR Berghofer

A mutant Tat protein inhibits infection of human cells by strains from diverse HIV-1 subtypes

Abstract

Background: Nullbasic is a mutant HIV-1 Tat protein that inhibits HIV-1 replication via three independent mechanisms that disrupts 1) reverse transcription of the viral RNA genome into a DNA copy, 2) HIV-1 Rev protein function required for viral mRNA transport from the nucleus to the cytoplasm and 3) HIV-1 mRNA transcription by RNA Polymerase II. The Nullbasic protein is derived from the subtype B strain HIV-1(BH10) and has only been tested against other HIV-1 subtype B strains. However, subtype B strains only account for similar to 10% of HIV-1 infections globally and HIV-1 Tat sequences vary between subtypes especially for subtype C, which is responsible for similar to 50% HIV-1 infection worldwide. These differences could influence the ability of Tat to interact with RNA and cellular proteins and thus could affect the antiviral activity of Nullbasic. Therefore, Nullbasic was tested against representative HIV-1 strains from subtypes C, D and A/D recombinant to determine if it can inhibit their replication.

Authors Rustanti, Lina; Jin, Hongping; Lor, Mary; Lin, Min Hsuan; Rawle, Daniel J.; Harrich, David
Journal VIROLOGY JOURNAL
Pages
Volume 14
Date 1/03/2017
Grant ID 1085359
Funding Body National Health and Medical Research Council Project
URL http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1186/s12985-017-0705-9