期刊
AIDS
卷 22, 期 14, 页码 1749-1757出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAD.0b013e328308937c
关键词
CD4-independence; HIV-1; human hepatocytes; human hepatoma cells
资金
- JSPS
- Ministry of Health and Welfare, Japan
Objective: HIV-1 isolates are prominently CD4-dependent and, to date, only a few laboratory-adapted CD4-independent strains have been reported. Therefore, whether CD4-independent viruses may exist in HIV-1-infected patients has remained unclear. Here, we report the successful isolation of a CD4-independent clinical HIV-1 strain, designated SDA-1, from the viral quasispecies of a therapy-naive HIV-1 and Pneumocystis jirovecii pneumonia patient in the late-stage of AIDS with extremely low CD4 cell count (CD4 = 1/mu l). We characterized this virus and further explored whether it could infect or induce pathological effects in human hepatocytes. Design and methods: To determine coreceptor usage and CD4-independent infection, the HIV-1 envelope (Env)-pseudotypes and Env-chimeric viruses were used. Results: SDA-1 was able to infect CD4(-) cell lines through either chemokine (C-X-C motif) receptor 4 or CCR5. It still maintained the ability to infect CD4(+) cells through Multiple coreceptors of chemokine (C-X-C motif) receptor 4, chemokine (C-C motif) receptor 5, chemokine (C-C motif) receptor 3 and chemokine (C-C motif) receptor 8. Productive infection by SDA-1 was noted in both CD4-negative hepatoma cells and primary Cultured human hepatocytes. Moreover, we demonstrated that SDA-1 could efficiently infect human hepatocytes on both static and mitotic phases through chemokine (C-X-C motif) receptor 4, without inducing apoptotic cell death. Conclusion: The present study provides evidence that emergence of CD4-independent HIV-1 virus in vivo may occur in HIV-1-infected patients. In addition, these results shed light on the mechanisms involved in liver damage in HIV-1-infected individuals, which could have important implications concerning the range of mutability and the pathogenesis of AIDS. (C) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
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