title: P-body components LSM1, GW182, DDX3, DDX6 and XRN1 are recruited to WNV replication sites and positively regulate viral replication.
abstract: In mammalian cells, proteins involved in mRNA silencing and degradation localize to discrete cytoplasmic foci called processing or P-bodies. Here we show that microscopically visible P-bodies are greatly diminished following West Nile viral infection, but the component proteins are not depleted. On the other hand, many P-body components including LSM1, GW182, DDX3, DDX6 and XRN1, but not others like DCP1a and EDC4 are recruited to the viral replication sites, as evidenced by their colocalization at perinuclear region with viral NS3. Kinetic studies suggest that the component proteins are first released from P-bodies in response to WNV infection within 12 h post-infection, followed by recruitment to the viral replication sites by 24-36 h post-infection. Silencing of the recruited proteins individually with siRNA interfered with viral replication to varying extents suggesting that the recruited proteins are required for efficient viral replication. Thus, the P-body proteins might provide novel drug targets for inhibiting viral infection.
authors.affiliation: Center of Excellence in Infectious Disease Research, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.
authors.forename: Harendra S
authors.initials: HS
authors.lastname: Chahar
authors.forename: Shuiping
authors.initials: S
authors.lastname: Chen
authors.forename: N
authors.initials: N
authors.lastname: Manjunath
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D006224:Cricetinae; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D005095:Exoribonucleases / Q000235:genetics / Q000378:metabolism; D040362:Geographic Information Systems; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D020365:RNA Helicases / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology*; D014901:West Nile Fever / Q000378:metabolism*; D014902:West Nile virus / Q000254:growth & development* / Q000378:metabolism*; D043583:Nucleoside-Triphosphatase; D000085242:Viral Proteases
chemical_list: D001324:Autoantigens; D053487:DEAD-box RNA Helicases; D005095:Exoribonucleases; D008869:Microtubule-Associated Proteins; D011518:Proto-Oncogene Proteins; D020365:RNA Helicases; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D012697:Serine Endopeptidases; D017361:Viral Nonstructural Proteins; C464824:LSM1 protein, human; C060028:NS3 protein, flavivirus; D043583:Nucleoside-Triphosphatase; D000085242:Viral Proteases; C465663:TNRC6A protein, human; C470512:XRN1 protein, human; C119332:DDX3X protein, human; C094683:DDX6 protein, human