HIV-1 and Ebola virus encode small peptide motifs that recruit Tsg101 to sites of particle assembly to facilitate egress.
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.
Martin-Serrano
J
J
Aaron Diamond AIDS Research Center and The Rockefeller University, New York, New York, USA.
Zang
T
T
Bieniasz
P D
PD
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000378:metabolism; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism*; D029043:Ebolavirus / Q000502:physiology*; D056827:Endosomal Sorting Complexes Required for Transport; D011992:Endosomes / Q000378:metabolism; D015683:Gene Products, gag / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009698:Nucleoproteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D014157:Transcription Factors / Q000378:metabolism*; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism*; D019065:Virus Assembly; D054301:gag Gene Products, Human Immunodeficiency Virus; D000099177:Tsg101 Protein
D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D015683:Gene Products, gag; D009698:Nucleoproteins; D014157:Transcription Factors; D014758:Viral Core Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; D000099177:Tsg101 Protein; C084819:nucleoprotein VP40, Ebola virus; C083002:p6 gag protein, Human immunodeficiency virus 1