title: Nonstructural Protein 4 of Porcine Reproductive and Respiratory Syndrome Virus Modulates Cell Surface Swine Leukocyte Antigen Class I Expression by Downregulating β2-Microglobulin Transcription.
abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) is the causative agent of PRRS, which has important impacts on the pig industry. PRRSV infection results in disruption of the swine leukocyte antigen class I (SLA-I) antigen presentation pathway. In this study, highly pathogenic PRRSV (HP-PRRSV) infection inhibited transcription of the β2-microglobulin (β2M) gene (B2M) and reduced cellular levels of β2M, which forms a heterotrimeric complex with the SLA-I heavy chain and a variable peptide and plays a critical role in SLA-I antigen presentation. HP-PRRSV nonstructural protein 4 (Nsp4) was involved in the downregulation of β2M expression. Exogenous expression of Nsp4 downregulated β2M expression at both the mRNA and the protein level and reduced SLA-I expression on the cell surface. Nsp4 bound to the porcineB2Mpromoter and inhibited its transcriptional activity. Domain III of Nsp4 and the enhancerPAMelement of the porcineB2Mpromoter were identified as essential for the interaction between Nsp4 andB2MThese findings demonstrate a novel mechanism whereby HP-PRRSV may modulate the SLA-I antigen presentation pathway and provide new insights into the functions of HP-PRRSV Nsp4.IMPORTANCEPRRSV modulates the host response by disrupting the SLA-I antigen presentation pathway. We show that HP-PRRSV downregulates SLA-I expression on the cell surface via transcriptional inhibition ofB2Mexpression by viral Nsp4. The interaction between domain III of Nsp4 and the enhancerPAMelement of the porcineB2Mpromoter is essential for inhibitingB2Mtranscription. These observations reveal a novel mechanism whereby HP-PRRSV may modulate SLA-I antigen presentation and provide new insights into the functions of viral Nsp4.
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, People's Republic of China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Qi
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, People's Republic of China.
authors.forename: Ke
authors.initials: K
authors.lastname: Liu
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, People's Republic of China.
authors.forename: Jianchao
authors.initials: J
authors.lastname: Wei
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, People's Republic of China.
authors.forename: Yuming
authors.initials: Y
authors.lastname: Li
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, People's Republic of China.
authors.forename: Beibei
authors.initials: B
authors.lastname: Li
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, People's Republic of China.
authors.forename: Donghua
authors.initials: D
authors.lastname: Shao
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, People's Republic of China.
authors.forename: Zhuanchang
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, People's Republic of China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, People's Republic of China.
authors.forename: Guangzhi
authors.initials: G
authors.lastname: Tong
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, People's Republic of China yafengq@shvri.ac.cn zhiyongma@shvri.ac.cn.
authors.forename: Yafeng
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Science, Shanghai, People's Republic of China yafengq@shvri.ac.cn zhiyongma@shvri.ac.cn.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Ma
mesh_terms: D000818:Animals; D002460:Cell Line; D015536:Down-Regulation; D015870:Gene Expression; D020868:Gene Silencing / Q000276:immunology; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000378:metabolism; D054884:Host-Pathogen Interactions; D019318:Porcine Reproductive and Respiratory Syndrome / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D019316:Porcine respiratory and reproductive syndrome virus / Q000502:physiology*; D011401:Promoter Regions, Genetic; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D059748:Proteolysis; D034421:Sus scrofa; D013552:Swine; D017361:Viral Nonstructural Proteins; D001613:beta 2-Microglobulin / Q000235:genetics* / Q000378:metabolism
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D017361:Viral Nonstructural Proteins; D001613:beta 2-Microglobulin; C438668:swine leukocyte antigen; D046988:Proteasome Endopeptidase Complex
keywords: Nsp4; PRRSV; SLA-I; porcine B2M promoter; porcine reproductive and respiratory syndrome virus; β2-microglobulin