Porcine reproductive and respiratory syndrome virus nsp4-mediated 82M downregulation contributes to SLA-I decrease and virus infection in vivo and in vitro

文献类型： 外文期刊

第一作者： Kang, Lei

作者： Kang, Lei;Su, Shuo;Qi, Pengfei;Qiu, Yafeng;Wei, Jianchao;Li, Beibei;Shao, Donghua;Li, Zongjie;Liu, Ke;Ma, Zhiyong;Wahaab, Abdul

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关键词： Porcine reproductive and respiratory syndrome; virus; nsp4; 82-microglobulin; SLA-I; CTL; Persistent infection

期刊名称：VIROLOGY （ 影响因子：3.7； 五年影响因子：3.2 ）

ISSN： 0042-6822

年卷期： 2024 年 595 卷

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收录情况： SCI

摘要： 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 8 2-microglobulin ( 8 2M) 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 8 2M and SLA-I expression. Almost all nsp4 mutants exogenously expressed in cells showed an attenuated effect on inhibition of 8 2M 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 8 2M 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 8 2M downregulation improved 8 2M/SLA-I expression in pigs.

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