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Ebola virus particle formation and budding are mediated by the VP40 protein, which possesses overlapping PTAP and PPXY late domain motifs (7-PTAPPXY-13). These late domain motifs have also been found in the Gag proteins of retroviruses and the matrix proteins of rhabdo- and arenaviruses. While in vitro studies suggest a critical role for late domain motifs in the budding of these viruses, including Ebola virus, it remains unclear as to whether the VP40 late domains play a role in Ebola virus replication. Alteration of both late domain motifs drastically reduced VP40 particle formation in vitro. However, using reverse genetics, we were able to generate recombinant Ebola virus containing mutations in either or both of the late domains. Viruses containing mutations in one or both of their late domain motifs were attenuated by one log unit. Transmission and scanning electron microscopy did not reveal appreciable differences between the mutant and wild-type viruses released from infected cells. These findings indicate that the Ebola VP40 late domain motifs enhance virus replication but are not absolutely required for virus replication in cell culture.
Authors : Neumann Gabriele , Ebihara Hideki , Takada Ayato , Noda Takeshi , Kobasa Darwyn , Jasenosky Luke D , Watanabe Shinji , Kim Jin H , Feldmann Heinz , Kawaoka Yoshihiro ,
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WP1011: T Cell Receptor Signaling Pathway
WP1025: B Cell Receptor Signaling Pathway
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 ITCH E3 Ubiquitin Ligase Interacts with Ebola Virus VP40 To Regulate Budding.
 Identification of continuous human B-cell epitopes in the VP35, VP40, nucleoprotein and glycoprotein of Ebola virus.
 Assembly of Ebola virus matrix protein VP40 is regulated by latch-like properties of N and C terminal tails.
 Mapping of a region of Ebola virus VP40 that is important in the production of virus-like particles.
 Role for amino acids 212KLR214 of Ebola virus VP40 in assembly and budding.
 Budding of PPxY-containing rhabdoviruses is not dependent on host proteins TGS101 and VPS4A.
 Overlapping motifs (PTAP and PPEY) within the Ebola virus VP40 protein function independently as late budding domains: involvement of host proteins TSG101 and VPS-4.
 HIV-1 and Ebola virus encode small peptide motifs that recruit Tsg101 to sites of particle assembly to facilitate egress.
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