自噬是宿主防御病毒感染的重要生物学过程。然而,许多病毒已经进化出各种策略来破坏宿主的抗病毒系统。猪繁殖与呼吸综合征病毒(PRRSV)是一种典型的免疫抑制病毒,对养猪业具有巨大的经济影响。目前,研究PRRSV在自噬过程中的逃逸机制,特别是通过伴侣介导的自噬(CMA),是有限的。这项研究证实,PRRSV糖蛋白5(GP5)可以通过抑制MTORC2/PHLPP1/GFAP通路破坏GFAP-LAMP2A复合物的形成,促进pGFAP-EF1α复合物的解离,并阻断LAMP2A的K63连接的聚泛素化以抑制CMA的活性。进一步的研究表明,CMA通过拮抗非结构蛋白11(NSP11)介导的I型干扰素(IFN-I)信号传导抑制发挥抗PRRSV作用。一起来看,这些结果表明PRRSVGP5通过靶向LAMP2A抑制CMA的抗病毒作用.这项研究为CMA中免疫抑制病毒的逃逸机制提供了新的见解。
目的:病毒已经进化出复杂的机制来操纵自噬以逃避降解和免疫反应。猪繁殖与呼吸综合征病毒(PRRSV)是一种典型的免疫抑制病毒,在养猪业造成巨大的经济损失。然而,PRRSV操纵自噬以防御宿主抗病毒作用的机制尚不清楚.在这项研究中,我们发现PRRSVGP5与LAMP2A相互作用并破坏GFAP-LAMP2A复合物的形成,从而抑制CMA的活性,随后增强NSP11介导的IFN-I信号通路的抑制作用,最终促进PRRSV复制。我们的研究揭示了PRRSV通过CMA逃避宿主抗病毒作用的新机制,提供潜在的主机目标,LAMP2A,用于开发抗病毒药物并有助于了解免疫抑制病毒的逃逸机制。
Autophagy is an important biological process in host defense against viral infection. However, many viruses have evolved various strategies to disrupt the host antiviral system. Porcine reproductive and respiratory syndrome virus (PRRSV) is a typical immunosuppressive virus with a large economic impact on the swine industry. At present, studies on the escape mechanism of PRRSV in the autophagy process, especially through chaperone-mediated autophagy (CMA), are limited. This study confirmed that PRRSV glycoprotein 5 (GP5) could disrupt the formation of the GFAP-
LAMP2A complex by inhibiting the MTORC2/PHLPP1/GFAP pathway, promoting the dissociation of the pGFAP-EF1α complex, and blocking the K63-linked polyubiquitination of
LAMP2A to inhibit the activity of CMA. Further research demonstrated that CMA plays an anti-PRRSV role by antagonizing nonstructural protein 11 (NSP11)-mediated inhibition of type I interferon (IFN-I) signaling. Taken together, these results indicate that PRRSV GP5 inhibits the antiviral effect of CMA by targeting
LAMP2A. This research provides new insight into the escape mechanism of immunosuppressive viruses in CMA.
OBJECTIVE: Viruses have evolved sophisticated mechanisms to manipulate autophagy to evade degradation and immune responses. Porcine reproductive and respiratory syndrome virus (PRRSV) is a typical immunosuppressive virus that causes enormous economic losses in the swine industry. However, the mechanism by which PRRSV manipulates autophagy to defend against host antiviral effects remains unclear. In this study, we found that PRRSV GP5 interacts with
LAMP2A and disrupts the formation of the GFAP-
LAMP2A complex, thus inhibiting the activity of CMA and subsequently enhancing the inhibitory effect of the NSP11-mediated IFN-I signaling pathway, ultimately facilitating PRRSV replication. Our study revealed a novel mechanism by which PRRSV escapes host antiviral effects through CMA, providing a potential host target,
LAMP2A, for developing antiviral drugs and contributing to understanding the escape mechanism of immunosuppressive viruses.