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HIV-1 and Ebola virus encode small peptide motifs that recruit Tsg101 to sites of particle assembly to facilitate egress

Nature Medicine volume 7, pages 1313–1319 (2001)Cite this article

Abstract

Retroviral Gag proteins encode sequences, termed late domains, which facilitate the final stages of particle budding from the plasma membrane. We report here that interactions between Tsg101, a factor involved in endosomal protein sorting, and short peptide motifs in the HIV-1 Gag late domain and Ebola virus matrix (EbVp40) proteins are essential for efficient egress of HIV-1 virions and Ebola virus-like particles. EbVp40 recruits Tsg101 to sites of particle assembly and a short, EbVp40-derived Tsg101-binding peptide sequence can functionally substitute for the HIV-1 Gag late domain. Notably, recruitment of Tsg101 to assembling virions restores budding competence to a late-domain–defective HIV-1 in the complete absence of viral late domain. These studies define an essential virus–host interaction that is conserved in two unrelated viruses. Because the Tsg101 is recruited by small, conserved viral sequence motifs, agents that mimic these structures are potential inhibitors of the replication of these lethal human pathogens.

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Figure 1: Correlative mutagenesis establishes the functional importance of the HIV-1 Gag–Tsg101 interaction.
Figure 2: A PTAP motif in Ebola virus Vp40 is required for the formation of virus-like particles and for Tsg101 binding.
Figure 3: EbVp40 induces the relocalization of Tsg101 to sites of particle assembly.
Figure 4: Short sequences derived from HIV-1 p6 and EbVp40 and containing the PTAP motif bind Tsg101, and the EbVp40 sequence functionally substitutes for the HIV-1 L-domain.
Figure 5: An L-domain–defective HIV-1 can be complemented in trans by recruitment of homologous or heterologous late domains or Tsg101-binding peptides to the site of particle assembly.
Figure 6: Recruitment of Tsg101 to sites of HIV-1 particle assembly rescues virion budding in the absence of a viral L-domain.

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Acknowledgements

We thank K. Li for technical assistance; H.-D. Klenk for the EbVp40 cDNA; N. Landau, P. Charneau, B. Chesebro and H. Chen for providing P4/R5 and the 183-H12-5C hybridoma cell lines through the AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH; and B. Mulder and M. Muesing for antibodies and helpful discussions. This work was supported by the Donald A. Pels Charitable Trust, The Columbia-Rockefeller Center for AIDS Research, and by a grant from the NIAID AI50111 (to P.D.B). J.M.-S. is the recipient of a Postdoctoral Fellowship from the Spanish Ministerio de Educación, Cultura y Deporte.

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  1. Aaron Diamond AIDS Research Center and The Rockefeller University, New York, New York, USA

    Juan Martin-Serrano, Trinity Zang & Paul D. Bieniasz

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Correspondence to Paul D. Bieniasz.

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Martin-Serrano, J., Zang, T. & Bieniasz, P. HIV-1 and Ebola virus encode small peptide motifs that recruit Tsg101 to sites of particle assembly to facilitate egress. Nat Med 7, 1313–1319 (2001). https://doi.org/10.1038/nm1201-1313

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