title: Differentiation of Th subsets inhibited by nonstructural proteins of respiratory syncytial virus is mediated by ubiquitination.
abstract: Human respiratory syncytial virus (RSV), a major cause of severe respiratory diseases, constitutes an important risk factor for the development of subsequent asthma. However, the mechanism underlying RSV-induced asthma is poorly understood. Viral non-structural proteins NS1 and NS2 are critically required for RSV virulence; they strongly suppress IFN-mediated innate immunity of the host cells. In order to understand the effects of NS1 and NS2 on differentiation of Th subsets, we constructed lentiviral vectors of NS1 or NS2 to infect 16 HBE and analyzed the expression of HLA-DR, CD80 and CD86 and differentiation of Th1, Th2 and Th17 by Flow Cytometric Analysis and real-time PCR. The results showed that NS1 inhibited expression of HLA-DR, CD80 and CD86 and differentiation of Th1, Th2 and Th17 lymphocytes, which could be reversed by deleting elongin C binding domain. NS2 inhibited the differentiation of Th2 and Th17, which was reversed by proteasome inhibitors of PS-341. Our results indicated that NS1 inhibited the differentiation of T lymphocytes through its mono-ubiquitination to interacted proteins, while NS2 inhibited differentiation of Th2 and Th17 through ubiquitin-proteasome pathway, which may be related with the susceptibility to asthma after RSV infection.
authors.affiliation: Respiratory Department, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Qin
authors.affiliation: Department of Basic Medicine, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Peng
authors.affiliation: Respiratory Department, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Chengping
authors.initials: C
authors.lastname: Hu
authors.affiliation: Department of Basic Medicine, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Department of Basic Medicine, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
authors.forename: Yigang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Basic Medicine, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
authors.forename: Yurong
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Department of Basic Medicine, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
authors.forename: Xiaoqun
authors.initials: X
authors.lastname: Qin
mesh_terms: D018122:B7-1 Antigen / Q000737:chemistry / Q000378:metabolism; D051940:B7-2 Antigen / Q000737:chemistry / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D057809:HEK293 Cells; D006684:HLA-DR Antigens / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D017434:Protein Structure, Tertiary; D018357:Respiratory Syncytial Virus Infections / Q000473:pathology / Q000821:virology; D018113:Respiratory Syncytial Virus, Human / Q000378:metabolism*; D018417:Th1 Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D054875:Ubiquitination; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D006684:HLA-DR Antigens; D017361:Viral Nonstructural Proteins