Characterization of a CD4-independent clinical HIV-1 that can efficiently infect human hepatocytes through chemokine (C-X-C motif) receptor 4

Peng Xiao, Osamu Usami, Yasuhiro Suzuki, Hong Ling, Nobuaki Shimizu, Hiroo Hoshino, Min Zhuang, Yugo Ashino, Hongxi Gu, Toshio Hattori

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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/μl). 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.

Original languageEnglish
Pages (from-to)1749-1757
Number of pages9
JournalAIDS
Volume22
Issue number14
DOIs
Publication statusPublished - 2008 Sep 12

Keywords

  • CD4-independence
  • HIV-1
  • Human hepatocytes
  • Human hepatoma cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Xiao, P., Usami, O., Suzuki, Y., Ling, H., Shimizu, N., Hoshino, H., Zhuang, M., Ashino, Y., Gu, H., & Hattori, T. (2008). Characterization of a CD4-independent clinical HIV-1 that can efficiently infect human hepatocytes through chemokine (C-X-C motif) receptor 4. AIDS, 22(14), 1749-1757. https://doi.org/10.1097/QAD.0b013e328308937c