Porcine Reproductive and Respiratory Syndrome Virus nsp1β Stabilizes HIF-1α to Enhance Viral Replication

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) has devastated the swine industry worldwide for over 30 years and shows no signs of slowing down. In this study, we found that PRRSV infection elevated hypoxia-inducible factor 1α (HIF-1α) expression.

Highly pathogenic PRRSV upregulates IL-13 production through nonstructural protein 9–mediated inhibition of N6-methyladenosine demethylase FTO

“…PRRSV proteins play important roles in the expression of a variety of proinflammatory factors and are involved in the process of immune response, antiviral infection, immune evasion, and pathogenesis ( 11 , 51 , 52 , 56 , 57 , 58 ). PRRSV infection can increase the HIF-1α levels, contributing to the development of inflammation and viral life cycle ( 11 ).…”

“…PRRSV proteins play important roles in the expression of a variety of proinflammatory factors and are involved in the process of immune response, antiviral infection, immune evasion, and pathogenesis ( 11 , 51 , 52 , 56 , 57 , 58 ). PRRSV infection can increase the HIF-1α levels, contributing to the development of inflammation and viral life cycle ( 11 ). One of the major properties of PRRSV nsp1β is the N-terminal nuclease activity and C-terminal deubiquitinating enzyme activity, while PRRSV nsp9 can downregulate PON1 to inhibit type-I IFN signaling pathway, eventually facilitating PRRSV replication ( 58 ).…”

“…The PRRSV genome contains 11 ORFs, encoding eight structural proteins and 16 nonstructural proteins (nsp), each possessing diverse functions in various steps of infection, replication, virulence, and virus–host interactions ( 3 , 4 , 5 , 6 , 7 , 8 ). Immunosuppression after PRRSV infection may contribute to inefficient innate and acquired immune responses, modulating the expression and release of inflammatory and/or anti-inflammatory factors, upregulating immunosuppressive cytokines expression, and allowing the viruses to rapidly reproduce and cause disease ( 9 , 10 , 11 , 12 ).…”

“…PRRSV infection has been reported to modulate various inflammatory factors and mediators, including cold-inducible RNA-binding protein, interleukin (IL)-17, IL-6, hypoxia-inducible factor 1a (HIF-1a), C1QBP, etc. ( 10 , 11 , 12 , 13 , 14 , 15 ). The enzymatic domains of PRRSV nonstructural protein 1β (nsp1β) nuclease protease and papain-like cysteine protease have been noted to elevate HIF-1a expression, thus facilitating viral proliferation ( 11 ).…”

“…( 10 , 11 , 12 , 13 , 14 , 15 ). The enzymatic domains of PRRSV nonstructural protein 1β (nsp1β) nuclease protease and papain-like cysteine protease have been noted to elevate HIF-1a expression, thus facilitating viral proliferation ( 11 ). Cold-inducible RNA-binding protein has been detected in stress granules as an RNA-binding protein, which positively regulates the NF-κB pathway to induce the expression of downstream proinflammatory cytokines, thus promoting inflammatory response during PRRSV infection ( 13 ).…”