Journal
MICROBES AND INFECTION
Volume 17, Issue 5, Pages 378-386Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.micinf.2015.02.002
Keywords
HIV; Humanized mice; CD4(+) T cells; CCR5
Categories
Funding
- Ministry of Education, Science, Sports and Culture of Japan
- Ministry of Health, Labor and Welfare of Japan
- Japan Foundation for AIDS Prevention
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CCR5-tropic (R5) immunodeficiency virus type 1 (HIV-1) strains are highly transmissible during the early stage of infection in humans, whereas CXCR4-tropic (X4) strains are less transmissible. This study aimed to explore the basis for early phase R5 and X4 HIV-1 infection in vivo by using humanized mice dually challenged with R5 HIV-1(NLAD8-D) harboring DsRed and X4 HIV-1(NL-E) harboring EGFP. Whereas R5 HIV-1 replicated well, X4 HIV-1 caused only transient viremia with variable kinetics; however, this was distinct from the low level but persistent viremia observed in mice challenged with X4 HIV-1 alone. Flow cytometric analysis of HIV-1-infected cells revealed that X4 HIV-1 infection of CCR5(+)CD4(+) T cells was significantly suppressed in the presence of R5 HIV-1. X4 HIV-1 was more cytopathic than R5 HIV-1; however, this was not the cause of restricted X4 HIV-1 infection because there were no significant differences in the mortality rates of CCR5(+) and CCR5(-) cells within the X4 HIV-1-infected cell populations. Taken together, these results suggest that restricted infection of CCR5(+)CD4(+) T cells by X4 (occurring via a still-to-be-identified mechanism) might contribute to the preferential transmission of R5 HIV-1 during the early phase of infection. (C) 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
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