کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3425181 1227272 2011 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Mutational pathways and genetic barriers to CXCR4-mediated entry by human immunodeficiency virus type 1
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ویروس شناسی
پیش نمایش صفحه اول مقاله
Mutational pathways and genetic barriers to CXCR4-mediated entry by human immunodeficiency virus type 1
چکیده انگلیسی

To examine mutational pathways that lead to CXCR4 use of HIV-1, we analyzed the genotypic and phenotypic characteristics of envelope sequences from a large panel of patient virus populations and individual clones containing different V3 mutations. Basic amino acid substitutions at position 11 were strong determinants of CXCR4-mediated entry but required multiple compensatory mutations to overcome associated reductions in infectivity. In contrast, basic amino acid substitutions at position 25, or substitutions at positions 6–8 resulting in the loss of a potential N-linked glycosylation site, contributed to CXCR4-mediated entry but required additional substitutions acting cooperatively to confer efficient CXCR4 use. Our assumptions, based upon examination of patient viruses, were largely confirmed by characterizing the coreceptor utilization of five distinct panels of isogenic envelope sequences containing V3 amino acid substitutions introduced by site-directed mutagenesis. These results further define the mutational pathways leading to CXCR4 use and their associated genetic barriers.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Virology - Volume 409, Issue 2, 20 January 2011, Pages 308–318
نویسندگان
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