Exostosin glycosyltransferase 1 reduces porcine reproductive and respiratory syndrome virus infection through proteasomal degradation of nsp3 and nsp5.
Exostosin glycosyltransferase 1 reduces porcine reproductive and respiratory syndrome virus infection through proteasomal degradation of nsp3 and nsp5.
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Exostosin 糖基转移酶 1 通过 nsp3 和 nsp5 的蛋白酶体降解减少猪繁殖与呼吸综合征病毒感染。
DOI：
10.1016/j.jbc.2021.101548
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Guo C
中科院分区：
文献类型：
--
作者：
Zhang X;Dong W;Wang X;Zhu Z;He S;Zhang H;Chen Y;Liu X;Guo C
Porcine reproductive and respiratory syndrome virus (PRRSV) continues to be a serious threat to the swine industry worldwide. Exostosin glycosyltransferase 1 (EXT1), an enzyme involved in the biosynthesis of heparin sulfate, has also been reported to be a host factor essential for a wide variety of pathogens. However, the role of EXT1 in PRRSV infection remains uncharted. Here, we identified that PRRSV infection caused an increase of EXT1 expression. EXT1 knockdown promoted virus infection, whereas its overexpression inhibited virus infection, suggesting an inhibitory function of EXT1 to PRRSV infection. We found that EXT1 had no effects on the attachment, internalization, or release of PRRSV but did restrict viral RNA replication. EXT1 was determined to interact with viral nonstructural protein 3 (nsp3) and nsp5 via its N-terminal cytoplasmic tail and to enhance K48-linked polyubiquitination of these two nsps to promote their degradation. Furthermore, the C-terminal glycosyltransferase activity domain of EXT1 was necessary for nsp3 and nsp5 degradation. We also found that EXT2, a EXT1 homolog, interacted with EXT1 and inhibited PRRSV infection. Similarly, EXT1 effectively restricted porcine epidemic diarrhea virus and porcine enteric alphacoronavirus infection in Vero cells. Taken together, this study reveals that EXT1 may serve as a broad-spectrum host restriction factor and suggests a molecular basis for the potential development of therapeutics against PRRSV infection.
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影响因子：
5
作者：
Gorbalenya AE;Enjuanes L;Ziebuhr J;Snijder EJ
通讯作者：
Snijder EJ
影响因子：
5
作者：
Fang Y;Snijder EJ
通讯作者：
Snijder EJ
DOI：
10.1016/j.bbagen.2018.01.002
发表时间：
2018-04-01
影响因子：
3
作者：
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通讯作者：
Kitagawa, Hiroshi
影响因子：
6.4
作者：
Angelini MM;Akhlaghpour M;Neuman BW;Buchmeier MJ
通讯作者：
Buchmeier MJ
影响因子：
4.8
作者：
Pedersen, LC;Dong, J;Negishi, M
通讯作者：
Negishi, M