1. Humanized mice dually challenged with R5 and X4 HIV-1 show preferential R5 viremia and restricted X4 infection of CCR5+CD4+ T cells
- Author
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Seiji Okada, Manabu Ato, Yasuko Tsunetsugu-Yokota, Mie Kobayashi-Ishihara, Shota Ikeno, Kazutaka Terahara, and Masayuki Ishige
- Subjects
CD4-Positive T-Lymphocytes ,Receptors, CXCR4 ,Receptors, CCR5 ,Immunology ,Cell ,Human immunodeficiency virus (HIV) ,Viremia ,Biology ,Virus Replication ,medicine.disease_cause ,Microbiology ,Immunodeficiency virus ,Green fluorescent protein ,Mice ,In vivo ,medicine ,Animals ,virus diseases ,Persistent viremia ,medicine.disease ,Virology ,Infectious Diseases ,medicine.anatomical_structure ,HIV-1 ,Early phase - 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.
- Published
- 2015