PMC:4576194 / 1199-5154 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/4576194","sourcedb":"PMC","sourceid":"4576194","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4576194","text":"1. Introduction\nClassical swine fever virus (CSFV), together with bovine viral diarrhea virus (BVDV) and border disease virus (BDV), is a member of the genus Pestivirus within the family Flaviviridae and an important pathogen of pigs that often causes huge economic losses to the pig industry worldwide. CSFV is a small enveloped virus with a single-stranded, positive-sense RNA genome of 12.3 kb. The RNA genome contains a single large open reading frame (ORF) coding for a polyprotein, flanked by a 5ʹ-untranslated region (UTR) and a 3ʹ-UTR. Under cellular and viral protease processing, the polyprotein is processed into 11 mature proteins, including four structural proteins (C, Erns, E1 and E2) and seven nonstructural proteins (Npro, p7, NS2-3, NS4A, NS4B, NS5A and NS5B) [1,2,3]. The 5ʹ-UTR contains an internal ribosome entry site (IRES) that is responsible for translation initiation of the viral genome [4]. The 3ʹ-UTR is in charge of regulating the pestiviral genome replication [5,6].\nThe CSFV NS5A comprises 497 amino acids and is a component of the replication complex. The conserved sequence C2717–C2740–C2742–C2767 in the NS5A protein has been proved to be important for viral growth and RNA synthesis [7]. It has been shown that NS5A regulates viral RNA replication through binding to NS5B (viral RNA-dependent RNA polymerase [RdRp]) and 3ʹ-UTR [8]. The NS5A protein of hepatitis C virus (HCV), another member of the family Flaviviridae, is an essential component of the replication complex [9] and plays a role in regulating cellular and viral mRNA translation [10,11]. The HCV NS5A–Core interaction is critical for the subcellular localization of NS5A and the production of infectious virus [12]. The HCV NS5A also plays an essential role in the switch from genome replication to particle assembly [13,14]. In addition, the CSFV NS5A decreases IRES-mediated translation in a dose-dependent manner and the key sites (K399, T401, E406 and L413) are also found in BVDV, BDV and HCV [15]. To date, studies have been focused on the roles of the CSFV NS5A protein in viral genomic replication and translation [8,15], but knowledge of NS5A-interacting host proteins and their impacts on CSFV replication is limited.\nThe eukaryotic elongation factor 1A (eEF1A), one of the most abundant protein synthesis factors, constitutes 1% to 4% of the total soluble proteins in actively dividing cells [16,17]. The canonical function of eEF1A is to bind aminoacyl-tRNA (aa-tRNA) in a GTP-dependent manner and deliver it to the A site on the ribosome during protein synthesis [18]. eEF1A is also involved in non-canonical functions including turnover of misfolded proteins, nuclear export events, binding and bundling of the actin cytoskeleton, apoptosis and the viral life cycle [19,20]. eEF1A contains three well-defined domains: the domain I binds to GTP; the domain II binds to the aminoacyl end of aa-tRNA, the domains I and II bind to the eEF1B complex, and the domain III is linked to actin binding [19].\nDifferent groups of viruses, such as tombusvirus (TBSV), human immunodeficiency type 1 (HIV-1) and West Nile virus (WNV), utilize eEF1A as cofactor for viral transcription, translation and assembly. For TBSV, eEF1A facilitates the assembly of the TBSV replicase and stimulates minus-strand synthesis [21]. The HIV-1 Nef protein enhances the resistance to stress-induced apoptosis in primary human macrophages through the nuclear–cytoplasmic transport of eEF1A and tRNAs. Moreover, eEF1 complex subunits are critical HIV-1 reverse transcription cofactors [22,23]. In addition, the BVDV NS5A was also shown to interact with eEF1A [24]. Considering CSFV, BVDV, HCV and WNV are all Flaviviridae members, we suppose that the CSFV NS5A protein possibly interacts with eEF1A or affects the CSFV growth in host cells. In this study, we identified the host protein eEF1A as a novel NS5A-interacting partner that negatively regulates the growth of CSFV.","divisions":[{"label":"Title","span":{"begin":0,"end":15}}],"tracks":[{"project":"2_test","denotations":[{"id":"26266418-10785320-144197513","span":{"begin":779,"end":780},"obj":"10785320"},{"id":"26266418-11967318-144197514","span":{"begin":914,"end":915},"obj":"11967318"},{"id":"26266418-15373834-144197515","span":{"begin":991,"end":992},"obj":"15373834"},{"id":"26266418-15994806-144197516","span":{"begin":993,"end":994},"obj":"15994806"},{"id":"26266418-19713054-144197517","span":{"begin":1219,"end":1220},"obj":"19713054"},{"id":"26266418-22795973-144197518","span":{"begin":1363,"end":1364},"obj":"22795973"},{"id":"26266418-15339921-144197519","span":{"begin":1509,"end":1510},"obj":"15339921"},{"id":"26266418-15784895-144197520","span":{"begin":1580,"end":1582},"obj":"15784895"},{"id":"26266418-18728014-144197521","span":{"begin":1583,"end":1585},"obj":"18728014"},{"id":"26266418-18524832-144197522","span":{"begin":1711,"end":1713},"obj":"18524832"},{"id":"26266418-19264615-144197523","span":{"begin":1818,"end":1820},"obj":"19264615"},{"id":"26266418-21525356-144197524","span":{"begin":1821,"end":1823},"obj":"21525356"},{"id":"26266418-19710255-144197525","span":{"begin":1999,"end":2001},"obj":"19710255"},{"id":"26266418-22795973-144197526","span":{"begin":2123,"end":2124},"obj":"22795973"},{"id":"26266418-19710255-144197527","span":{"begin":2125,"end":2127},"obj":"19710255"},{"id":"26266418-2211674-144197528","span":{"begin":2404,"end":2406},"obj":"2211674"},{"id":"26266418-7610475-144197529","span":{"begin":2407,"end":2409},"obj":"7610475"},{"id":"26266418-20444696-144197530","span":{"begin":2577,"end":2579},"obj":"20444696"},{"id":"26266418-21964468-144197531","span":{"begin":2781,"end":2783},"obj":"21964468"},{"id":"26266418-22555874-144197532","span":{"begin":2784,"end":2786},"obj":"22555874"},{"id":"26266418-21964468-144197533","span":{"begin":3007,"end":3009},"obj":"21964468"},{"id":"26266418-21079685-144197534","span":{"begin":3313,"end":3315},"obj":"21079685"},{"id":"26266418-22476100-144197535","span":{"begin":3567,"end":3569},"obj":"22476100"},{"id":"26266418-22628567-144197536","span":{"begin":3570,"end":3572},"obj":"22628567"},{"id":"26266418-11714969-144197537","span":{"begin":3641,"end":3643},"obj":"11714969"}],"attributes":[{"subj":"26266418-10785320-144197513","pred":"source","obj":"2_test"},{"subj":"26266418-11967318-144197514","pred":"source","obj":"2_test"},{"subj":"26266418-15373834-144197515","pred":"source","obj":"2_test"},{"subj":"26266418-15994806-144197516","pred":"source","obj":"2_test"},{"subj":"26266418-19713054-144197517","pred":"source","obj":"2_test"},{"subj":"26266418-22795973-144197518","pred":"source","obj":"2_test"},{"subj":"26266418-15339921-144197519","pred":"source","obj":"2_test"},{"subj":"26266418-15784895-144197520","pred":"source","obj":"2_test"},{"subj":"26266418-18728014-144197521","pred":"source","obj":"2_test"},{"subj":"26266418-18524832-144197522","pred":"source","obj":"2_test"},{"subj":"26266418-19264615-144197523","pred":"source","obj":"2_test"},{"subj":"26266418-21525356-144197524","pred":"source","obj":"2_test"},{"subj":"26266418-19710255-144197525","pred":"source","obj":"2_test"},{"subj":"26266418-22795973-144197526","pred":"source","obj":"2_test"},{"subj":"26266418-19710255-144197527","pred":"source","obj":"2_test"},{"subj":"26266418-2211674-144197528","pred":"source","obj":"2_test"},{"subj":"26266418-7610475-144197529","pred":"source","obj":"2_test"},{"subj":"26266418-20444696-144197530","pred":"source","obj":"2_test"},{"subj":"26266418-21964468-144197531","pred":"source","obj":"2_test"},{"subj":"26266418-22555874-144197532","pred":"source","obj":"2_test"},{"subj":"26266418-21964468-144197533","pred":"source","obj":"2_test"},{"subj":"26266418-21079685-144197534","pred":"source","obj":"2_test"},{"subj":"26266418-22476100-144197535","pred":"source","obj":"2_test"},{"subj":"26266418-22628567-144197536","pred":"source","obj":"2_test"},{"subj":"26266418-11714969-144197537","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#eceb93","default":true}]}]}}