Terahara Kazutaka, Ishige Masayuki, Ikeno Shota, Okada Seiji, Kobayashi-Ishihara Mie, Ato Manabu, Tsunetsugu-Yokota Yasuko
Department of Immunology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
Department of Immunology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
Microbes Infect. 2015 May;17(5):378-86. doi: 10.1016/j.micinf.2015.02.002. Epub 2015 Apr 1.
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.
CCR5嗜性（R5）1型免疫缺陷病毒（HIV-1）毒株在人类感染早期具有高度传染性，而CXCR4嗜性（X4）毒株的传染性较低。本研究旨在通过使用双重感染携带DsRed的R5 HIV-1NLAD8-D和携带EGFP的X4 HIV-1（NL-E）的人源化小鼠，探索R5和X4 HIV-1在体内早期感染的基础。虽然R5 HIV-1复制良好，但X4 HIV-1仅引起具有可变动力学的短暂病毒血症；然而，这与单独用X4 HIV-1攻击的小鼠中观察到的低水平但持续的病毒血症不同。对HIV-1感染细胞的流式细胞术分析显示，在存在R5 HIV-1的情况下，X4 HIV-1对CCR5(+)CD4(+) T细胞的感染受到显著抑制。X4 HIV-1比R5 HIV-1更具细胞病变性；然而，这并不是X4 HIV-1感染受限的原因，因为在X4 HIV-1感染的细胞群体中，CCR5(+)和CCR5(-)细胞的死亡率没有显著差异。综上所述，这些结果表明，X4 HIV-1对CCR5(+)CD4(+) T细胞的感染受限（通过一种尚待确定的机制发生）可能有助于R5 HIV-在感染早期的优先传播。
