Immune reconstitution of the female reproductive tract of humanized BLT mice and their susceptibility to human immunodeficiency virus infection

Abstract

An HIV vaccine capable of providing sterilizing immunity from vaginal infection would reduce the spread of HIV to women. Unfortunately, only one of the four HIV-1 vaccine clinical trials has demonstrated any level of protection (31%) against HIV-1 transmission. Additionally, only one topical microbicide clinical trial has reported an overall reduction in HIV transmission (39%). Developing even more effective vaccines and microbicides will require a better understanding of the key events involved in HIV infection and dissemination at the site of exposure. Novel immunodeficient mice capable of being systemically reconstituted with human hematopoietic stem cells have provided new systems where HIV transmission studies can be performed. Specifically, a humanized mouse model of vaginal HIV transmission has been developed that utilizes the humanized bone marrow-liver-thymus (BLT) mouse. The female reproductive tract (FRT) of humanized BLT mice is reconstituted with functional human immune cells rendering them susceptible to vaginal HIV-1 infection. In this review we focus on four aspects of BLT mice for the study of vaginal HIV-1 transmission: (1) we discuss methods for creating humanized BLT mice and their reconstitution with human hematopoietic cells, (2) we describe reconstitution of the BLT mouse FRT with human immune cells, (3) we highlight the work done regarding vaginal HIV-1 transmission and (4) we summarize the efficacy of systemic pre-exposure prophylaxis (PrEP) to prevent vaginal HIV-1 transmission in BLT mice. BLT mice are a highly relevant small animal model for studying vaginal HIV-1 transmission, prevention and therapy.