Human parainfluenza virus type 3(HPIV3), a member of the Paramyxoviridae family, can cause lower respiratory disease in infants and young children. The phosphoprotein(P) of HPIV3 is an essential cofactor of the viral ...Human parainfluenza virus type 3(HPIV3), a member of the Paramyxoviridae family, can cause lower respiratory disease in infants and young children. The phosphoprotein(P) of HPIV3 is an essential cofactor of the viral RNA-dependent RNA polymerase large protein(L). P connects nucleocapsid protein(N) with L to initiate genome transcription and replication.Sumoylation influences many important pathways of the target proteins, and many viral proteins are also themselves sumoylated. In this study, we found that the P of HPIV3 could be sumoylated, and mutation of K492 and K532 to arginine(PK492 R/K532 R) failed to be sumoylated within P, which enhances HPIV3 minigenome activity. Biochemical studies showed that PK492 R/K532 Rhad no effect on its interactions with N, formation of homo-tetramers and formation of inclusion bodies.Finally, we found that incorporation of K492 R/K532 R into a recombinant HPIV3(rHPIV3-PK492 R/K532 R) increased viral production in culture cells, suggesting that sumoylation attenuates functions of P and down-regulates viral replication.展开更多
基金supported by grants from National Key R&D Program of China (2017YFA0505801)the National Natural Science Foundation of China (81825015, 81871650 and 31630086)+2 种基金National Science and Technology Major Project (2018ZX10101004)the Natural Science Foundation of Hubei Province Innovation Group (2017CFA022)Advanced Customer Cultivation Project of Wuhan National Biosafety Laboratory (2019ACCP-MS06)。
文摘Human parainfluenza virus type 3(HPIV3), a member of the Paramyxoviridae family, can cause lower respiratory disease in infants and young children. The phosphoprotein(P) of HPIV3 is an essential cofactor of the viral RNA-dependent RNA polymerase large protein(L). P connects nucleocapsid protein(N) with L to initiate genome transcription and replication.Sumoylation influences many important pathways of the target proteins, and many viral proteins are also themselves sumoylated. In this study, we found that the P of HPIV3 could be sumoylated, and mutation of K492 and K532 to arginine(PK492 R/K532 R) failed to be sumoylated within P, which enhances HPIV3 minigenome activity. Biochemical studies showed that PK492 R/K532 Rhad no effect on its interactions with N, formation of homo-tetramers and formation of inclusion bodies.Finally, we found that incorporation of K492 R/K532 R into a recombinant HPIV3(rHPIV3-PK492 R/K532 R) increased viral production in culture cells, suggesting that sumoylation attenuates functions of P and down-regulates viral replication.
