Interfering Residues Narrow the Spectrum of MLV Restriction by Human TRIM5α

PLoS Pathogens

Priscilla Turelli¹  Séverine Reynard¹  Didier Trono¹  Fatima Serhan¹  Pierre V Maillard¹ 

[1] Global Health Institute, School of Life Sciences, “Frontiers in Genetics” National Center for Competence in Research, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland

关键词: Viral packaging;    HIV-1;    Amino acid substitution;    Alanine;    Infectious disease control;    Polymerase chain reaction;    Vector-borne diseases;    Arginine;   

DOI  :  10.1371/journal.ppat.0030200

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

TRIM5α is a restriction factor that limits infection of human cells by so-called N- but not B- or NB-tropic strains of murine leukemia virus (MLV). Here, we performed a mutation-based functional analysis of TRIM5α-mediated MLV restriction. Our results reveal that changes at tyrosine336 of human TRIM5α, within the variable region 1 of its C-terminal PRYSPRY domain, can expand its activity to B-MLV and to the NB-tropic Moloney MLV. Conversely, we demonstrate that the escape of MLV from restriction by wild-type or mutant forms of huTRIM5α can be achieved through interdependent changes at positions 82, 109, 110, and 117 of the viral capsid. Together, our results support a model in which TRIM5α-mediated retroviral restriction results from the direct binding of the antiviral PRYSPRY domain to the viral capsid, and can be prevented by interferences exerted by critical residues on either one of these two partners.

【 授权许可】

CC BY