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
Background： Although human parainfluenza virus （HPIV） has been determined as an important viral cause of acute respiratory infections （ARIs） in infants and young children, data on long-term investigation are stil...Background： Although human parainfluenza virus （HPIV） has been determined as an important viral cause of acute respiratory infections （ARIs） in infants and young children, data on long-term investigation are still lacking to disclose the infection pattern of HPIV in China. Methods： Nasopharyngeal aspirates were collected from 25,773 hospitalized pediatric patients with ARIs from January 2004 through December 2012 for respiratory virus screen by direct immuno-fluorescence assay. Results： Out of these specimens, 1675 （6.50%, 1675/25,773） showed HPIV positive, including 261 （1.01%, 261/25,773） for HPIVI, 28 （0.11%, 28/25,773） for HPIV2, and 1388 （5.39%, 1388/25373） for HPIV3, 2 of the samples were positive for both HPIV1 and HPIV3, and 36 were co-detected with other viruses. The positive rates of HPIVs were higher in those younger than 3 years old. HPIV3 was detected from all age groups, predominantly from patients under 3 years of age, and the highest frequency was found in those 6 months to 1-year old （352/4077, 8.63%）. HPlV3 was the dominant type in each of the years detected between May and July. HPIV1 showed a peak in every odd year, mainly in August or September. HPIV was detected most frequently from patients with upper respiratory infection （12.49%, 157/1257）, followed by bronchitis （ 11.13%, 176/2479）, asthma （9.31%, 43/462）, bronchiolitis （5.91%, 150/2536）, pneumonia （6.06%, 1034/17,068）, and those with underlying diseases （1.0%, 15/1506）. HPIV3 is the dominant type in these six disease groups referred above, especially in the asthma group. Conclusions： HPIV is one of the important viral causes of ARIs in infants and young children in Beijing based on the data from the hospitalized children covering a 9-year term. HPIV3 is the predominant type in all these years and in most of the disease groups. HPIVs with different types show different seasonality.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.
文摘Background： Although human parainfluenza virus （HPIV） has been determined as an important viral cause of acute respiratory infections （ARIs） in infants and young children, data on long-term investigation are still lacking to disclose the infection pattern of HPIV in China. Methods： Nasopharyngeal aspirates were collected from 25,773 hospitalized pediatric patients with ARIs from January 2004 through December 2012 for respiratory virus screen by direct immuno-fluorescence assay. Results： Out of these specimens, 1675 （6.50%, 1675/25,773） showed HPIV positive, including 261 （1.01%, 261/25,773） for HPIVI, 28 （0.11%, 28/25,773） for HPIV2, and 1388 （5.39%, 1388/25373） for HPIV3, 2 of the samples were positive for both HPIV1 and HPIV3, and 36 were co-detected with other viruses. The positive rates of HPIVs were higher in those younger than 3 years old. HPIV3 was detected from all age groups, predominantly from patients under 3 years of age, and the highest frequency was found in those 6 months to 1-year old （352/4077, 8.63%）. HPlV3 was the dominant type in each of the years detected between May and July. HPIV1 showed a peak in every odd year, mainly in August or September. HPIV was detected most frequently from patients with upper respiratory infection （12.49%, 157/1257）, followed by bronchitis （ 11.13%, 176/2479）, asthma （9.31%, 43/462）, bronchiolitis （5.91%, 150/2536）, pneumonia （6.06%, 1034/17,068）, and those with underlying diseases （1.0%, 15/1506）. HPIV3 is the dominant type in these six disease groups referred above, especially in the asthma group. Conclusions： HPIV is one of the important viral causes of ARIs in infants and young children in Beijing based on the data from the hospitalized children covering a 9-year term. HPIV3 is the predominant type in all these years and in most of the disease groups. HPIVs with different types show different seasonality.
