Study of a novel hypervariable region in hepatitis C virus (HCV) E2 envelope glycoprotein

被引：48

作者：

Troesch, Myriam

Meunier, Isabelle

Lapierre, Pascal

Lapointe, Nonnand

Alvarez, Fernando

Boucher, Marc

Soudeyns, Hugo

机构：

[1] CHU Mere Enfant St Justine, Ctr Rech, Unite Immunopathol Virale, Montreal, PQ H3T 1C5, Canada

[2] CHU Mere Enfant St Justine, Ctr Rech, Serv Gastroenterol Hepatol & Nutr, Montreal, PQ H3T 1C5, Canada

[3] CHU Mere Enfant St Justine, Ctr Rech, Ctr Maternal & Infantile SIDA, Montreal, PQ H3T 1C5, Canada

[4] Univ Montreal, Dept Microbiol & Immunol, Montreal, PQ H3C 3J7, Canada

[5] Univ Montreal, Program Biomed Sci, Montreal, PQ H3C 3J7, Canada

[6] Univ Montreal, Dept Pediat, Montreal, PQ H3C 3J7, Canada

[7] Univ Montreal, Dept Gynecol & Obstet, Montreal, PQ H3C 3J7, Canada

来源：

VIROLOGY | 2006年 / 352卷 / 02期

关键词：

hepatitis C virus; quasispecies; envelope; positive selection; molecular modeling;

D O I：

10.1016/j.virol.2006.05.015

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

A large share of hepatitis C virus amino acid sequence variation is concentrated within two hypervariable regions located at the N-tertninus of the E2 envelope glycoprotein (HVR1 and HVR2). Interhost and intrahost comparison of 391 E2 sequences derived from 17 subjects infected with HCV using amino acid entropy revealed clustering of amino acid variability at a third site (residues 431-466), which was termed HVR3. Genetic distance analysis supported the division of HVR3 into three subdomains (HVR3a, HVR3b, and HVR3c). Study of synonymous and nonsynonymous nucleic acid substitutions confirmed that HVR3a was subjected to strong intrahost-selective pressure. Physicochemical and antigenicity predictions, conservation of key residues, and molecular modeling were concordant with one another and further validated the proposed organization of HVR3. Taken together, these results are suggestive of a role for HVR3 in cell surface receptor binding and viral entry akin to that proposed for HVR1 and HVR2. (c) 2006 Elsevier Inc. All rights reserved.

引用

页码：357 / 367

页数：11

共 67 条

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