• ja CD4-independent human immunodeficiency virus infection involves participation of endocytosis and cathepsin B.
    • Yoshii, Hiroaki
    • Kamiyama, Haruka
    • Goto, Kensuke
    • Oishi, Kazunori
    • Katunuma, Nobuhiko
    • Tanaka, Yuetsu
    • Hayashi, Hideki
    • Matsuyama, Toshifumi
    • Sato, Hironori
    • Yamamoto, Naoki
    • Kubo, Yoshinao
  • © 2011 Yoshii et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
  • Other During a comparison of the infectivity of mNDK, a CD4-independent human immunodeficiency virus type 1 (HIV-1) strain, to various cell lines, we found that HeLa cells were much less susceptible than 293T and TE671 cells. Hybridoma cells between HeLa and 293T cells were as susceptible as 293T cells, suggesting that cellular factors enhance the mNDK infection in 293T cells. By screening a cDNA expression library in HeLa cells, cystatin C was isolated as an enhancer of the mNDK infection. Because cathepsin B protease, a natural ligand of cystatin C, was upregulated in HeLa cells, we speculated that the high levels of cathepsin B activities were inhibitory to the CD4-independent infection and that cystatin C enhanced the infection by impairing the excessive cathepsin B activity. Consistent with this idea, pretreatment of HeLa cells with 125 µM of CA-074Me, a cathepsin B inhibitor, resulted in an 8-fold enhancement of the mNDK infectivity. Because cathepsin B is activated by low pH in acidic endosomes, we further examined the potential roles of endosomes in the CD4-independent infection. Suppression of endosome acidification or endocytosis by inhibitors or by an Eps15 dominant negative mutant reduced the infectivity of mNDK in which CD4-dependent infections were not significantly impaired. Taken together, these results suggest that endocytosis, endosomal acidification, and cathepsin B activity are involved in the CD4-independent entry of HIV-1.
  • Other identifier:PLoS One, 6(4), e19352; 2011
Publisher Public Library of Science
    Created2020-12-22 , Issued2011-04-25
  • eng
Resource Type journal article
Version Type VoR
Identifier URI
  • isIdenticalTo PMID 21541353
  • isIdenticalTo DOI
    • ISSN 1932-6203
      • PLoS One 6(4), e19352
Oaidate 2021-02-17