2012
DOI: 10.1128/jvi.06711-11
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The PSAP Motif within the ORF3 Protein of an Avian Strain of the Hepatitis E Virus Is Not Critical for Viral InfectivityIn Vivobut Plays a Role in Virus Release

Abstract: The ORF3 protein of hepatitis E virus (HEV) is a multifunctional protein important for virus replication. The ORF3 proteins from human, swine, and avian strains of HEV contain a conserved PXXP amino acid motif, resembling either Src homology 3 (SH3) cell signaling interaction motifs or “late domains” involved in host cell interactions aiding in particle release. Using an avian strain of HEV, we determined the roles of the conserved prolines within the PREPSAPP motif in HEV replication and infectivity in Leghor… Show more

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Cited by 51 publications
(42 citation statements)
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“…The C-terminal part of vp13 contains a proline-rich sequence that interacts with the Src homology 3 domain of cellular proteins (47). The PSAP motif of avian HEV was found to play a role in virus release in vivo though not to be essential for virus infectivity (48). We constructed vp13 with PSAP mutations, and our preliminary study with these mutant proteins indicates that the PSAP motif appears not to correlate with vp13 enhancement of IFN induction (data not shown).…”
Section: Discussionmentioning
confidence: 99%
“…The C-terminal part of vp13 contains a proline-rich sequence that interacts with the Src homology 3 domain of cellular proteins (47). The PSAP motif of avian HEV was found to play a role in virus release in vivo though not to be essential for virus infectivity (48). We constructed vp13 with PSAP mutations, and our preliminary study with these mutant proteins indicates that the PSAP motif appears not to correlate with vp13 enhancement of IFN induction (data not shown).…”
Section: Discussionmentioning
confidence: 99%
“…ORF2 codes for the viral capsid protein. ORF3 encodes a small multifunctional phosphoprotein that interacts with host cellular proteins and may have a role in HEV virion release from the host cell (8)(9)(10). ORF1 encodes an approximately 186-kDa polyprotein with the following domain structure: NH 2 -methyltransferase (11), cysteine protease (12,13), polyproline hypervariable region (HVR) (14,15), ADP-ribose phosphorylase (X or macro domain), helicase (16,17), and RNA-dependent RNA polymerase (RdRp) (18)-COOH.…”
mentioning
confidence: 99%
“…ORF3 protein can be phosphorylated on serine 71, and this phosphorylated form interacts with non-glycosylated capsid protein potentially playing a role in virion assembly 69 . ORF3 protein is found throughout the host cell but accumulates in filamentous patterns corresponding to its interaction with microtubules 70 and in punctate arrangements corresponding to early and recycling endosomes 71, 72 . Monoclonal antibodies against ORF3 protein can recognize HEV particles from cell culture supernatants and serum of infected patients but not virus from the feces, suggesting that ORF3 is only present on the surface of nascent HEV virions 73 .…”
Section: Hepatitis E and Its Causative Agent Hepatitis E Virusmentioning
confidence: 99%
“…The ORF3 protein of HEV has a PSAP motif that is important for release of HEV particles through interaction with the host ESCRT protein TSG101 72, 127 . Many enveloped viruses utilize late domains 128 to interact with ESCRT proteins and pinch off from the infected host cell.…”
Section: Potential Therapeutic Targets Against Hevmentioning
confidence: 99%