tailieunhanh - Báo cáo y học: " The role of the N-terminal segment of CCR5 in HIV-1 Env-mediated membrane fusion and the mechanism of virus adaptation to CCR5 lacking this segment"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học 'Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: " The role of the N-terminal segment of CCR5 in HIV-1 Env-mediated membrane fusion and the mechanism of virus adaptation to CCR5 lacking this segment. | BioMed Central Retrovirology Research Open Access The role of the N-terminal segment of CCR5 in HIV-I Env-mediated membrane fusion and the mechanism of virus adaptation to CCR5 lacking this segment Gregory B Melikyan 1 Emily J Platt2 and David Kabat2 Address Unstitute of Human Virology University of Maryland School of W. Lombard St. Baltimore MD 21201 USA and 2Department of Biochemistry and Molecular Biology Oregon Health and Science University Portland OR 97239 USA Email Gregory B Melikyan - melikian@ Emily J Platt - platte@ David Kabat - kabat@ Corresponding author Published 8 August 2007 Received 20 June 2007 Retrovirology 2007 4 55 doi 1742-4690-4-55 Accepted 8 August 2007 This article is available from http content 4 1 55 2007 Melikyan et al 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 HIV-1 envelope glycoprotein Env induces membrane fusion as a result of sequential binding to CD4 and chemokine receptors CCR5 or CXCR4 . The critical determinants of CCR5 coreceptor function are the N-terminal domain Nt and the second extracellular loop. However mutations in gp120 adapt HIV-1 to grow on cells expressing the N-terminally truncated CCR5 A18 Platt et al. J. Virol. 2005 79 4357-68 . Results We have functionally characterized the adapted Env designated Env NYP using a quantitative cell-cell fusion assay. The rate of fusion with target cells expressing wild-type CCR5 and the resistance to fusion inhibitors was virtually identical for wild-type Env and Env NYP implying that the coreceptor affinity had not increased as a result of adaptation. In contrast Env NYP -induced fusion with cells expressing CCR5 A18 occurred at a slower rate .