Vpr Mediates Immune Evasion and HIV-1 Spread.

HIV;Microbiology and Immunology;Health Sciences;Microbiology and Immunology

Collins, David R.Telesnitsky, Alice ;

University of Michigan

关键词: HIV;    Microbiology and Immunology;    Health Sciences;    Microbiology and Immunology;   

Others  :  https://deepblue.lib.umich.edu/bitstream/handle/2027.42/113293/davrcol_1.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

The molecular mechanisms by which human immunodeficiency virus (HIV-1) evades immunity to cause persistent infection remain incompletely characterized.Viral protein R (Vpr) is conserved in all primate lentiviruses, including HIV-1.Previous studies have demonstrated that Vpr is required for maximal infection of T lymphocytes in vivo.However, Vpr does not enhance HIV-1 infection of T lymphocytes under standard in vitro infection conditions, and the mechanism of Vpr function is poorly understood.Our work demonstrates that Vpr prevents the induction of a type I interferon-stimulated antiviral response in macrophages that targets Env and Env-containing virions for lysosomal degradation.By preventing this response, Vpr promotes Env-dependent virological synapse formation and enables efficient spread of HIV-1 from macrophages to activated T lymphocytes.This mode of spread requires direct cell-to-cell contact and is highly resistant to neutralizing antibodies.These studies provide a mechanistic explanation for the evolutionary conservation and function of Vpr.