TAILIEUCHUNG - Báo cáo y học: " Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: " Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein. | Retrovirology BioMed Central Research Open Access Second site escape of a T20-dependent HIV-1 variant by a single amino acid change in the CD4 binding region of the envelope glycoprotein Chris E Baldwin and Ben Berkhout Address Laboratory of Experimental Virology Department of Medical Microbiology Center for Infection and Immunity Amsterdam CINIMA Academic Medical Center of the University of Amsterdam The Netherlands Email Chris E Baldwin - Ben Berkhout - Corresponding author Published 29 November 2006 Received 13 October 2006 Accepted 29 November 2006 Retrovirology 2006 3 84 doi 1742-4690-3-84 This article is available from http content 3 1 84 2006 Baldwin and Berkhout licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License http licenses by which permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited. Abstract Background We previously described the selection of a T20-dependent human immunodeficiency virus type-1 HIV-1 variant in a patient on T20 therapy. The fusion inhibitor T20 targets the viral envelope Env protein by blocking a conformational switch that is critical for viral entry into the host cell. T20-dependent viral entry is the result of 2 mutations in Env GIA-SKY creating a protein that undergoes a premature conformational switch and the presence of T20 prevents this premature switch and rescues viral entry. In the present study we performed 6 independent evolution experiments with the T20-dependent HIV-1 variant in the absence of T20 with the aim to identify second site compensatory changes which may provide new mechanistic insights into Env function and the T20-dependence mechanism. Results Escape variants with improved replication capacity appeared within 42 days in 5 evolution cultures. Strikingly 3 cultures revealed the

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