1. Porcine reproductive and respiratory syndrome virus nsp4-mediated β2M downregulation contributes to SLA-I decrease and virus infection in vivo and in vitro.
- Author
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Kang, Lei, Wahaab, Abdul, Qi, Pengfei, Qiu, Yafeng, Wei, Jianchao, Li, Beibei, Shao, Donghua, Li, Zongjie, Liu, Ke, Ma, Zhiyong, and Su, Shuo
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PORCINE reproductive & respiratory syndrome , *VIRUS diseases , *GENE expression , *DOWNREGULATION - Abstract
Porcine reproductive and respiratory syndrome virus (PRRSV) infection inhibits swine leukocyte antigen class I (SLA-I) expression in pigs, resulting in inefficient antigen presentation and subsequent low levels of cellular PRRSV-specific immunity as well as persistent viremia. We previously observed that the non-structural protein 4 (nsp4) of PRRSV contributed to inhibition of the β2-microglobulin (β2M) and SLA-I expression in cells. Here, we constructed a series of nsp4 mutants with different combination of amino acid mutations to attenuate the inhibitory effect of nsp4 on β2M and SLA-I expression. Almost all nsp4 mutants exogenously expressed in cells showed an attenuated effect on inhibition of β2M and SLA-I expression, but the recombinant PRRSV harboring these nsp4 mutants failed to be rescued with exception of the rPRRSV-nsp4-mut10 harboring three amino acid mutations. However, infection of rPRRSV-nsp4-mut10 not only enhanced β2M and SLA-I expression in both cells and pigs but also promoted the DCs to active the CD3+CD8+T lymphocytes more efficiently, as compared with its parental PRRSV (rPRRVS-nsp4-wt). These data suggested that the inhibition of nsp4-mediated β2M downregulation improved β2M/SLA-I expression in pigs. • The Nsp4 gene of PRRSV on virus level inhibit the expression of β2M/SLA-I gene in pigs in this research filed. • The three amino acid sites of Nsp4 gene we have screened play a key role in inhibition of the expression of β2M/SLA-I gene in pigs. • The rPRRSV-nsp4-mut10 can induce more expression of β2M/SLA-I which accelerates the clearance of PRRSV in pigs. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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