Rhabdo-immunodeficiency virus, a murine model of acute HIV-1 infection

eLife

Emily J Mastrocola¹  Theodora Hatziioannou¹  Fabian Schmidt¹  Jessie R Willen²  Dennis Voronin²  Paul D Bieniasz²  Trinity M Zang²  Rachel A Liberatore²  Elena Cassella² 

[1] Howard Hughes Medical Institute, The Rockefeller University, New York, United States;Laboratory of Retrovirology, The Rockefeller University, New York, United States;

关键词: HIV-1;    antibody;    envelope;    CD4;    CCR5;    neutralization;   

DOI  :  10.7554/eLife.49875

来源: DOAJ

【 摘 要 】

Numerous challenges have impeded HIV-1 vaccine development. Among these is the lack of a convenient small animal model in which to study antibody elicitation and efficacy. We describe a chimeric Rhabdo-Immunodeficiency virus (RhIV) murine model that recapitulates key features of HIV-1 entry, tropism and antibody sensitivity. RhIVs are based on vesicular stomatitis viruses (VSV), but viral entry is mediated by HIV-1 Env proteins from diverse HIV-1 strains. RhIV infection of transgenic mice expressing human CD4 and CCR5, exclusively on mouse CD4+ cells, at levels mimicking those on human CD4+ T-cells, resulted in acute, resolving viremia and CD4+ T-cell depletion. RhIV infection elicited protective immunity, and antibodies to HIV-1 Env that were primarily non-neutralizing and had modest protective efficacy following passive transfer. The RhIV model enables the convenient in vivo study of HIV-1 Env-receptor interactions, antiviral activity of antibodies and humoral responses against HIV-1 Env, in a genetically manipulatable host.

【 授权许可】

Unknown