Humanized mice dually challenged with R5 and X4 HIV-1 show preferential R5 viremia and restricted X4 infection of CCR5(+)CD4(+) T cells.

Abstract

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-1NLAD8-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 HIV-1 (occurring via a still-to-be-identified mechanism) might contribute to the preferential transmission of R5 HIV-1 during the early phase of infection.

• Authors: Kazutaka Terahara, Masayuki Ishige, Shota Ikeno, Seiji Okada, Mie Kobayashi-Ishihara, Manabu Ato, Yasuko Tsunetsugu-Yokota
• Journal: Microbes and infection (Microbes Infect) Vol. 17 Issue 5 Pg. 378-86 (May 2015) ISSN: 1769-714X [Electronic] France
• PMID: 25839960 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Chemical References

• Receptors, CCR5
• Receptors, CXCR4

Topics

• Animals
• CD4-Positive T-Lymphocytes (cytology, virology)
• HIV-1 (immunology, pathogenicity)
• Mice
• Receptors, CCR5 (immunology)
• Receptors, CXCR4 (immunology)
• Viremia (mortality, pathology, transmission)
• Virus Replication (immunology)