The role of lysine residue at amino acid position 165 of human immunodeficiency virus type 1 CRF01_AE Gag in reducing viral drug susceptibility to protease inhibitors.

Recombinant human immunodeficiency virus type 1 (HIV-1) containing a CRF01_AE Gag, AE-Gag62, was significantly less susceptible to protease inhibitors (PIs) than the subtype B reference strain, NL4-3; therefore, the mechanism of how AE-Gag62 reduced viral drug susceptibility to PIs was studied in this report. The results showed that the lysine residue at amino acid position 165 (K165) of AE-Gag62 played a role in reducing the drug susceptibility of the recombinant virus to PIs. In addition, K165 potentially appears more frequently in CRF01_AE viruses than in the viruses of other major HIV-1 subtypes.

Short communication: RNA interference directed against Axin1 upregulates human immunodeficiency virus type 1 gene expression by activating the Wnt signaling pathway in HeLa-derived J111 cells.

Axin1, a regulator of Wnt signaling, was previously identified as playing a negative role in the late phase of human immunodeficiency virus type 1 (HIV-1) replication in HeLa-derived J111 cells. In this report, we studied the molecular mechanism of how Axin1 regulates HIV-1 replication. HIV-1 transactivator, Tat-dependent viral reporter gene expression was enhanced in J111 cells transfected with small interfering RNA (siRNA) against Axin1.

Impact of amino acid variations in Gag and protease of HIV type 1 CRF01_AE strains on drug susceptibility of virus to protease inhibitors.

Background: Protease (PR) inhibitors (PIs) were designed against subtype B virus of human immunodeficiency virus type 1 (HIV-1), but believed to retain its activity against most of the other subtypes. CRF01_AE PR (AE-PR) contains background mutations that are presumed to alter the drug susceptibility of PR. In addition, amino acid variations found in HIV-1 Gag potentially affect the drug susceptibility or catalytic efficiency of PR.