Differential level in co-down-modulation of CD4 and CXCR4 primed by HIV- 1 gp120 in response to phorbol ester, PMA, among HIV-1 isolates

Satoko Tahara-Hanaoka, Yuki Ushijima, Hiroshi Tarui, Masayuki Wada, Toshio Hara, Shigeo Imanishi, Tomoyuki Yamaguchi, Toshio Hattori, Hiromitsu Nakauchi, Atsushi Koito

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


HIV-1 enters cells through interacting with cell surface molecules such as CD4 and chemokine receptors. We generated recombinant soluble gp120s derived from T-cell line-tropic (T-tropic) and macrophage-tropic (M-tropic) HIV-1 strains using a baculovirus expression system and investigated the association of CD4-gp120 complex with the chemokine receptor and/or other surface molecule(s). For monitoring the co-down-modulations of the CD4-gp120 complex, a cytoplasmic domain deletion mutant (tailless CD4), which is not capable of undergoing down-modulation by itself in response to phorbol ester PMA, was used. Our studies revealed both cell-type and HIV-1 strain-specific differences. We found that T-tropic gp120s were capable of priming co-down- modulation with tailless CD4 by interacting with CXCR4, whereas M-tropic SF162 gp120 could not after PMA treatment even in the presence of CCR5. Among the T-tropic HIV-1 envelopes, IIIB gp120 was the most potent. Furthermore, the ability of gp120 to prime the PMA induced co-down-modulation of tailless CD4 appeared to be dependent on the concentration of the principal coreceptor CXCR4. Nevertheless, the observation that IIIB gp120 strongly primed tailless CD4 co-down-modulation on human osteosarcoma HOS cells that express undetectable levels of surface CXCR4 raised the possibility that membrane component(s) other than those recently identified can be involved in down- modulation of the CD4/gp120 complexes.

Original languageEnglish
Pages (from-to)489-498
Number of pages10
Issue number6
Publication statusPublished - 2000


  • Coreceptor
  • Down-modulation
  • HIV-1
  • Phorbol ester

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology


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