Functional interaction between the cytoplasmic leucine-zipper domain of HIV-1 gp41 and p115-RhoGEF

H. Zhang, L. Wang, S. Kao, I. P. Whitehead, M. J. Hart, B. Liu, K. Duus, K. Burridge, C. J. Der, L. Su

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Abstract

The long cytoplasmic tail of the human immunodeficiency virus (HIV)-I transmembrane protein gp41 (gp41C) is implicated in the replication and cytopathicity of HIV-1 [1]. Little is known about the specific functions of gp41C, however. HIV-1 or simian immunodeficiency virus (SIV) mutants with defective gp41C have cell-type- or species-dependent phenotypes [2-6]. Thus, host factors are implicated in mediating the functions of gp41C. We report here that gp41C interacted with the carboxy-terminal regulatory domain of p115-RhoGEF [7], a specific guanine nucleotide exchange factor (GEF) and activator of the RhoA GTPase, which regulates actin stress fiber formation, activation of serum response factor (SRF) and cell proliferation [8,9]. We demonstrate that gp41C inhibited p115-mediated actin stress fiber formation and activation of SRF. An amphipathic helix region with a leucine-zipper motif in gp41C is involved in its interaction with p115. Mutations in gp41C leading to loss of interaction with p115 impaired HIV-1 replication in human T cells. These findings suggest that an important function of gp41C is to modulate the activity of p115-RhoGEF and they thus reveal a new potential anti-HIV-1 target.

Original languageEnglish (US)
Pages (from-to)1271-1274
Number of pages4
JournalCurrent Biology
Volume9
Issue number21
StatePublished - Nov 4 1999
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Zhang, H., Wang, L., Kao, S., Whitehead, I. P., Hart, M. J., Liu, B., Duus, K., Burridge, K., Der, C. J., & Su, L. (1999). Functional interaction between the cytoplasmic leucine-zipper domain of HIV-1 gp41 and p115-RhoGEF. Current Biology, 9(21), 1271-1274.