Emergence of a Drug-Dependent Human Immunodeficiency Virus Type 1 Variant during Therapy with the T20 Fusion Inhibitor
AUTOR(ES)
Baldwin, Chris E.
FONTE
American Society for Microbiology
RESUMO
The fusion inhibitor T20 belongs to a new class of anti-human immunodeficiency virus type 1 (HIV-1) drugs designed to block entry of the virus into the host cell. However, the success of T20 has met with the inevitable emergence of drug-resistant HIV-1 variants. We describe an evolutionary pathway taken by HIV-1 to escape from the selective pressure of T20 in a treated patient. Besides the appearance of T20-resistant variants, we report for the first time the emergence of drug-dependent viruses with mutations in both the HR1 and HR2 domains of envelope glycoprotein 41. We propose a mechanistic model for the dependence of HIV-1 entry on the T20 peptide. The T20-dependent mutant is more prone to undergo the conformational switch that results in the formation of the fusogenic six-helix bundle structure in gp41. A premature switch will generate nonfunctional envelope glycoproteins (dead spikes) on the surface of the virion, and T20 prevents this abortive event by acting as a safety pin that preserves an earlier prefusion conformation.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=525057Documentos Relacionados
- Emergence of Resistant Human Immunodeficiency Virus Type 1 in Patients Receiving Fusion Inhibitor (T-20) Monotherapy
- THE DRUG-REQUIRING PHASE IN THE GROWTH OF DRUG-DEPENDENT ENTEROVIRUSES*
- Absence of the platelet receptor for drug-dependent antibodies in the Bernard-Soulier syndrome.
- Variant Human Immunodeficiency Virus Type 1 Proteases and Response to Combination Therapy Including a Protease Inhibitor
- The Assessment of Drug-Dependent and Isoimmune Antiplatelet Antibodies by the Use of Platelet Aggregometry
