TY - JOUR
T1 - Hyper-phosphorylation of nsp2-related proteins of porcine reproductive and respiratory syndrome virus
T2 - Hyper-phosphorylation of PRRSV nsp2 proteins
AU - Shang, Pengcheng
AU - Yuan, Fangfeng
AU - Misra, Saurav
AU - Li, Yanhua
AU - Fang, Ying
N1 - Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/4
Y1 - 2020/4
N2 - Viruses exploit phosphorylation of both viral and host proteins to support viral replication. In this study, we demonstrate that porcine reproductive and respiratory syndrome virus replicase nsp2, and two nsp2-related −2/−1 frameshifting products, nsp2TF and nsp2N, are hyper-phosphorylated. By mapping phosphorylation sites, we subdivide an extended, previously uncharacterized region, located between the papain-like protease-2 (PLP2) domain and frameshifting site, into three distinct domains. These domains include two large hypervariable regions (HVR) with putative intrinsically disordered structures, separated by a conserved and partly structured interval domain that we defined as the inter-HVR conserved domain (IHCD). Abolishing phosphorylation of the inter-species conserved residue serine918, which is located within the IHCD region, abrogates accumulation of viral genomic and subgenomic RNAs and recombinant virus production. Our study reveals the biological significance of phosphorylation events in nsp2-related proteins, emphasizes pleiotropic functions of nsp2-related proteins in the viral life cycle, and presents potential links to pathogenesis.
AB - Viruses exploit phosphorylation of both viral and host proteins to support viral replication. In this study, we demonstrate that porcine reproductive and respiratory syndrome virus replicase nsp2, and two nsp2-related −2/−1 frameshifting products, nsp2TF and nsp2N, are hyper-phosphorylated. By mapping phosphorylation sites, we subdivide an extended, previously uncharacterized region, located between the papain-like protease-2 (PLP2) domain and frameshifting site, into three distinct domains. These domains include two large hypervariable regions (HVR) with putative intrinsically disordered structures, separated by a conserved and partly structured interval domain that we defined as the inter-HVR conserved domain (IHCD). Abolishing phosphorylation of the inter-species conserved residue serine918, which is located within the IHCD region, abrogates accumulation of viral genomic and subgenomic RNAs and recombinant virus production. Our study reveals the biological significance of phosphorylation events in nsp2-related proteins, emphasizes pleiotropic functions of nsp2-related proteins in the viral life cycle, and presents potential links to pathogenesis.
KW - Hyper-phosphorylation
KW - Intrinsically disordered protein
KW - nsp2-related proteins
KW - PRRSV
KW - Subgenomic RNA
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U2 - 10.1016/j.virol.2020.01.018
DO - 10.1016/j.virol.2020.01.018
M3 - Article
C2 - 32174300
AN - SCOPUS:85079403575
SN - 0042-6822
VL - 543
SP - 63
EP - 75
JO - Virology
JF - Virology
ER -