Antagonizing Interferon-Mediated Immune Response by Porcine Reproductive and Respiratory Syndrome Virus

Interferons (IFNs) are important components in innate immunity involved in the first line of defense to protect host against viral infection. Porcine reproductive and respiratory syndrome virus (PRRSV) leads to severe economic losses for swine industry since being first identified in early 1990s. PRRSV interplays with host IFN production and IFN-activated signaling, which may contribute to the delayed onset and low level of neutralizing antibodies, as well as weak cell-mediated immune response in infected pigs. PRRSV encodes several proteins that act as antagonists for the IFN signaling. In this review, we summarized the various strategies used by PRRSV to antagonize IFN production and thwart IFN-activated antiviral signaling, as well as the variable interference with IFN-mediated immune response by different PRRSV strains. Thorough understanding of the interaction between PRRSV and host innate immune response will facilitate elucidation of PRRSV pathogenesis and development of a better strategy to control PRRS.

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The Function of the PRRSV–Host Interactions and Their Effects on Viral Replication and Propagation in Antiviral Strategies

Vaccines ◽

10.3390/vaccines9040364 ◽

2021 ◽

Vol 9 (4) ◽

pp. 364

Author(s):

Jun Ma ◽

Lulu Ma ◽

Meiting Yang ◽

Wei Wu ◽

Wenhai Feng ◽

...

Keyword(s):

Immune Response ◽

Molecular Mechanisms ◽

Immune Escape ◽

Rna Virus ◽

Economic Losses ◽

Respiratory Syndrome Virus ◽

Swine Industry ◽

Live Virus ◽

Virus Challenge ◽

Host Interactions

Porcine reproductive and respiratory syndrome virus (PRRSV) affects the global swine industry and causes disastrous economic losses each year. The genome of PRRSV is an enveloped single-stranded positive-sense RNA of approximately 15 kb. The PRRSV replicates primarily in alveolar macrophages of pig lungs and lymphatic organs and causes reproductive problems in sows and respiratory symptoms in piglets. To date, studies on how PRRSV survives in the host, the host immune response against viral infections, and pathogenesis, have been reported. PRRSV vaccines have been developed, including inactive virus, modified live virus, attenuated live vaccine, DNA vaccine, and immune adjuvant vaccines. However, there are certain problems with the durability and effectiveness of the licensed vaccines. Moreover, the high variability and fast-evolving populations of this RNA virus challenge the design of PRRSV vaccines, and thus effective vaccines against PRRSV have not been developed successfully. As is well known, viruses interact with the host to escape the host’s immune response and then replicate and propagate in the host, which is the key to virus survival. Here, we review the complex network and the mechanism of PRRSV–host interactions in the processes of virus infection. It is critical to develop novel antiviral strategies against PRRSV by studying these host–virus interactions and structures to better understand the molecular mechanisms of PRRSV immune escape.

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Porcine Reproductive and Respiratory Syndrome Virus Nonstructural Protein 1β Modulates Host Innate Immune Response by Antagonizing IRF3 Activation

Journal of Virology ◽

10.1128/jvi.01326-09 ◽

2009 ◽

Vol 84 (3) ◽

pp. 1574-1584 ◽

Cited By ~ 177

Author(s):

Lalit K. Beura ◽

Saumendra N. Sarkar ◽

Byungjoon Kwon ◽

Sakthivel Subramaniam ◽

Clinton Jones ◽

...

Keyword(s):

Immune Response ◽

Innate Immune Response ◽

Nuclear Translocation ◽

Sendai Virus ◽

Nonstructural Protein ◽

Adaptive Immune Response ◽

Inhibitory Effect ◽

Innate Immune ◽

Respiratory Syndrome Virus ◽

Host Innate Immune Response

ABSTRACT Porcine reproductive and respiratory syndrome virus (PRRSV) infection of swine leads to a serious disease characterized by a delayed and defective adaptive immune response. It is hypothesized that a suboptimal innate immune response is responsible for the disease pathogenesis. In the study presented here we tested this hypothesis and identified several nonstructural proteins (NSPs) with innate immune evasion properties encoded by the PRRS viral genome. Four of the total ten PRRSV NSPs tested were found to have strong to moderate inhibitory effects on beta interferon (IFN-β) promoter activation. The strongest inhibitory effect was exhibited by NSP1 followed by, NSP2, NSP11, and NSP4. We focused on NSP1α and NSP1β (self-cleavage products of NSP1 during virus infection) and NSP11, three NSPs with strong inhibitory activity. All of three proteins, when expressed stably in cell lines, strongly inhibited double-stranded RNA (dsRNA) signaling pathways. NSP1β was found to inhibit both IFN regulatory factor 3 (IRF3)- and NF-κB-dependent gene induction by dsRNA and Sendai virus. Mechanistically, the dsRNA-induced phosphorylation and nuclear translocation of IRF3 were strongly inhibited by NSP1β. Moreover, when tested in a porcine myelomonocytic cell line, NSP1β inhibited Sendai virus-mediated activation of porcine IFN-β promoter activity. We propose that this NSP1β-mediated subversion of the host innate immune response plays an important role in PRRSV pathogenesis.

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Porcine Epidemic Diarrhea Virus and the Host Innate Immune Response

Pathogens ◽

10.3390/pathogens9050367 ◽

2020 ◽

Vol 9 (5) ◽

pp. 367 ◽

Cited By ~ 1

Author(s):

Shasha Li ◽

Jinping Yang ◽

Zixiang Zhu ◽

Haixue Zheng

Keyword(s):

Immune Response ◽

Innate Immune Response ◽

Porcine Epidemic Diarrhea Virus ◽

Innate Immune ◽

Viral Rna ◽

Watery Diarrhea ◽

Economic Losses ◽

Diarrhea Virus ◽

Host Innate Immune Response ◽

Porcine Epidemic Diarrhea

Porcine epidemic diarrhea virus (PEDV), a swine enteropathogenic coronavirus (CoV), is the causative agent of porcine epidemic diarrhea (PED). PED causes lethal watery diarrhea in piglets, which has led to substantial economic losses in many countries and is a great threat to the global swine industry. Interferons (IFNs) are major cytokines involved in host innate immune defense, which induce the expression of a broad range of antiviral effectors that help host to control and antagonize viral infections. PEDV infection does not elicit a robust IFN response, and some of the mechanisms used by the virus to counteract the host innate immune response have been unraveled. PEDV evades the host innate immune response by two main strategies including: 1) encoding IFN antagonists to disrupt innate immune pathway, and 2) hiding its viral RNA to avoid the exposure of viral RNA to immune sensors. This review highlights the immune evasion mechanisms employed by PEDV, which provides insights for the better understanding of PEDV-host interactions and developing effective vaccines and antivirals against CoVs.

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