Determinants of human immunodeficiency virus type 1 baseline susceptibility to the fusion inhibitors enfuvirtide and T-649 reside outside the peptide interaction site

Journal of Virology
Marintha L HeilC A Derdeyn

Abstract

The peptide fusion inhibitor (PFI) enfuvirtide is the first of a new class of entry inhibitors to receive FDA approval. We previously determined the susceptibility of 55 PFI-naïve-patient isolates to enfuvirtide and a second peptide inhibitor, T-649. Seven of the 55 viral isolates were insusceptible to enfuvirtide, T-649, or both inhibitors in the absence of prior exposure. To determine the molecular basis of the insusceptible phenotypes, we PCR amplified and cloned five PFI-insusceptible and one PFI-susceptible, full-length, biologically functional env genes and characterized viruses pseudotyped with the Env proteins in a single-round drug sensitivity assay. Overall, the mean 50% inhibitory concentrations of enfuvirtide and T-649 for the PFI-insusceptible Env pseudotypes were 1.4 to 1.7 log(10) and 1.2 to 1.8 log(10) greater, respectively, than those for a PFI-susceptible lab strain, NLHX; however, all of the PFI-insusceptible Env proteins conserved the sequence of a critical enfuvirtide interaction site (residues 36 to 38 of gp41, GIV) in HR-1. In contrast, multiple amino acid changes were observed C-terminal to HR-1, many of which were located in regions of HR-2 corresponding to the PFI. Nevertheless, peptides based on patie...Continue Reading

References

Jan 1, 1978·Annual Review of Biochemistry·P Y Chou, G D Fasman
Nov 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·C WildT Matthews
May 1, 1995·Journal of Virology·H B BernsteinE Hunter
Dec 1, 1995·Nature Structural Biology·M LuP S Kim
May 22, 1997·Nature·W WeissenhornD C Wiley
Feb 12, 1998·Proceedings of the National Academy of Sciences of the United States of America·J K JudiceR S McDowell
Dec 23, 1998·Proceedings of the National Academy of Sciences of the United States of America·D C ChanP S Kim
May 20, 1999·Molecular Membrane Biology·T L Hoffman, R W Doms
May 9, 2001·Biochemistry·J L Cole, V M Garsky
Nov 6, 2002·Proceedings of the National Academy of Sciences of the United States of America·Samuel K SiaPeter S Kim
Nov 22, 2002·Proceedings of the National Academy of Sciences of the United States of America·Jacqueline D ReevesRobert W Doms
Dec 28, 2002·Journal of Virology·Béatrice LabrosseFabrizio Mammano
Apr 12, 2003·AIDS Research and Human Retroviruses·Thomas J KetasJohn P Moore
Jan 27, 2004·Antimicrobial Agents and Chemotherapy·N T ParkinC J Petropoulos

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Citations

Mar 3, 2007·AIDS Research and Human Retroviruses·Patrick W MobleyLarry M Gordon
Mar 31, 2009·AIDS Research and Human Retroviruses·Rebecca M LynchCynthia A Derdeyn
Oct 18, 2005·AIDS·Raghavan ChinnaduraiFrank Kirchhoff
Jan 17, 2008·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Yanjie YiRonald G Collman
Jul 21, 2010·Antimicrobial Agents and Chemotherapy·Emmanuel González-OrtegaJosé A Esté
Feb 8, 2013·Viruses·Leonardo Augusto Luvison Araújo, Sabrina E M Almeida
Jun 7, 2005·Expert Opinion on Emerging Drugs·Erik De Clercq
Jun 13, 2006·Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology·C SuG Heilek-Snyder
Jul 19, 2011·Biochimica Et Biophysica Acta·Avraham AshkenaziYechiel Shai
Sep 5, 2006·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Denis M TebitHans-Georg Krausslich
Jul 11, 2007·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Mary Anne TrabaudPatrice Andre
May 17, 2008·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Neerja Kaushik-BasuDylan Harris
Mar 15, 2018·Frontiers in Cellular and Infection Microbiology·Xiujuan ZhangYuxian He

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