Nie Chuanyi, Sato Kei, Misawa Naoko, Kitayama Hiroko, Fujino Hisanori, Hiramatsu Hidefumi, Heike Toshio, Nakahata Tatsutoshi, Tanaka Yuetsu, Ito Mamoru, Koyanagi Yoshio
Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, 53 Shogoinkawara-cho, Sakyo-ku, Kyoto, Kyoto 606-8507, Japan.
Virology. 2009 Nov 10;394(1):64-72. doi: 10.1016/j.virol.2009.08.011. Epub 2009 Sep 9.
To investigate the events leading to the depletion of CD4(+) T lymphocytes during long-term infection of human immunodeficiency virus type 1 (HIV-1), we infected human CD34(+) cells-transplanted NOD/SCID/IL-2Rgamma(null) mice with CXCR4-tropic and CCR5-tropic HIV-1. CXCR4-tropic HIV-1-infected mice were quickly depleted of CD4(+) thymocytes and both CD45RA(+) naïve and CD45RA(-) memory CD4(+) T lymphocytes, while CCR5-tropic HIV-1-infected mice were preferentially depleted of CD45RA(-) memory CD4(+) T lymphocytes. Staining of HIV-1 p24 antigen revealed that CCR5-tropic HIV-1 preferentially infected effector memory T lymphocytes (T(EM)) rather than central memory T lymphocytes. In addition, the majority of p24(+) cells in CCR5-tropic HIV-1-infected mice were activated and in cycling phase. Taken together, our findings indicate that productive infection mainly takes place in the activated T(EM) in cycling phase and further suggest that the predominant infection in T(EM) would lead to the depletion of memory CD4(+) T lymphocytes in CCR5-tropic HIV-1-infected mice.
为了研究人类免疫缺陷病毒1型（HIV-1）长期感染期间导致CD4(+) T淋巴细胞耗竭的事件，我们用趋化因子受体4（CXCR4）嗜性和趋化因子受体5（CCR5）嗜性的HIV-1感染了移植了人CD34(+)细胞的NOD/SCID/IL-2Rγ(null)小鼠。CXCR4嗜性HIV-1感染的小鼠的CD4(+)胸腺细胞以及CD45RA(+)初始和CD45RA(-)记忆性CD4(+) T淋巴细胞迅速耗竭，而CCR5嗜性HIV-1感染的小鼠中CD45RA(-)记忆性CD4(+) T淋巴细胞优先耗竭。HIV-1 p24抗原染色显示，CCR5嗜性HIV-1优先感染效应记忆T淋巴细胞（T(EM)）而非中枢记忆T淋巴细胞。此外，CCR5嗜性HIV-1感染的小鼠中大多数p24(+)细胞被激活并处于细胞周期。综上所述，我们的研究结果表明，有效感染主要发生在处于细胞周期的活化T(EM)中，并进一步表明T(EM)中的主要感染会导致CCR5嗜性HIV-1感染小鼠中记忆性CD4(+) T淋巴细胞的耗竭。
