Porcine Reproductive and Respiratory Syndrome Virus Adapts Antiviral Innate Immunity via Manipulating MALT1

Gu, Huiying; Zheng, Suya; Han, Guangwei; Yang, Haotian; Deng, Zhuofan; Liu, Zehui; He, Fang

doi:10.1128/mbio.00664-22

Cited by 18 publications

(12 citation statements)

References 58 publications

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“…Porcine reproductive and respiratory syndrome virus (PRRSV), a virulent pathogen of swine, suppresses the innate immune response and induces persistent infection [ 5 , 50 , 51 ]. More detailed reviews of host interactions with PRRSV conclude that most PRRSV strains delayed and impaired the adaptive immune response, inhibiting the release of pro-inflammatory cytokines, promoting anti-inflammatory cytokines, and modulating the activity and function of immune cells, including dendritic cells, macrophages, natural killer cells, T lymphocytes, and B lymphocytes [ 1 , 3 , 5 , 13 , 14 ]. PRRSV infection upregulates the expression of negative immune regulators including NF-k B inhibitors (NFKBIA, NFKBID, NFKBIZ, and TNFAIP3) and T-cell exhaustion markers (programmed death ligand-1 [PD-L1], PD-L2, interleukin-10 [IL-10], IDO1, and transforming growth factor b2 [TGFB2]) in PAMs to modulate the host’s immune response [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

“…Porcine reproductive and respiratory syndrome (PRRS), resulting from the porcine reproductive and respiratory syndrome virus (PRRSV), is one of the most important swine diseases threatening pigs’ health at all ages and causing substantial economic losses worldwide [ 1 ]. PRRSV is a positive-strand RNA virus belonging to the Arteriviridae family, whose genome has nine open reading frames and encodes seven structural proteins and 16 non-structural proteins [ 2 , 3 ]. During PRRSV infection, every viral protein could be associated with the immunomodulation capability of the virus.…”

Section: Introductionmentioning

confidence: 99%

“…During PRRSV infection, every viral protein could be associated with the immunomodulation capability of the virus. A typical characteristic of PRRSV infection in pigs is evading host defenses through the suppression of innate immunity [ 3 , 4 ]. The absence of a classical innate antiviral immune response occurs as a result of multiple strategies, such as influencing the production of inflammatory and immunomodulatory cytokines, suppressing or enhancing interferon production, enhancing immunosuppressive cytokine expression, or disturbing the development of immune cells including monocytes, macrophages, and T/B cells [ 1 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

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Porcine Reproductive and Respiratory Syndrome Virus Modulates the Switch of Macrophage Polarization from M1 to M2 by Upregulating MoDC-Released sCD83

Gong

Zhang

et al. 2023

Viruses

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Porcine reproductive and respiratory syndrome virus (PRRSV), the most economically important infectious disease of pigs, elicits poor innate and adaptive immune responses. Soluble CD83 (sCD83), a secretion from various immune cell populations, especially MoDCs, is involved in negatively regulating the immune response. We speculate sCD83 may be a critical factor in the process of PRRSV-coordinated macrophage polarization. In this study, we found that PAMs co-cultured with PRRSV-infected MoDCs inhibited the M1 macrophage while enhancing the M2 macrophage. This was accompanied by a decrease in the pro-inflammatory cytokine TNF-α and iNOS and an increase in the anti-inflammatory cytokine IL-10 and Arg1. Meanwhile, sCD83 incubation causes the same specific effects lead to a switch in macrophage from M1 to M2. Neutralization of sCD83 removes the inhibitory effects of PRRSV on PAMs. Using reverse genetics, we generated recombinant PRRSVs with mutations in N protein, nsp1α, and nsp10 (knockout sCD83-concerned key amino acid site). Four mutant viruses lost the suppression of M1 macrophage markers, in contrast to the restriction of the upregulation of M2 macrophage markers. These findings suggest that PRRSV modulates the switch of macrophage polarization from M1 to M2 by upregulating the MoDC-induced secretion of CD83, providing new insights into the mechanism by which PRRSV regulates host immunity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Porcine Reproductive and Respiratory Syndrome Virus Modulates the Switch of Macrophage Polarization from M1 to M2 by Upregulating MoDC-Released sCD83

Gong

Zhang

et al. 2023

Viruses

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“…Nsp1β is a stress-responsive protein, enters virusinduced stress granules (SGs) during infection, and repurposes SGs into a proviral platform, where it co-opts the SG core component G3BP1 to interact with PKR in a regulated manner (Gao et al, 2022). The latest research shows that PRRSV modulates mucosaassociated lymphoid tissue lymphoma translocation protein 1 (MALT1) expression to antagonize anti-PRRSV RNases N4BP1 and monocyte chemotactic protein-induced protein (MCPIP1) upon infection, thereby facilitating viral replication (Gu et al, 2022). PRRSV also significantly upregulates MCPIP1 expression in lungs of PRRSV-infected piglets, as well as in cells cultured in vitro to promote replication in the early stage of virus infection (Zheng et al, 2021).…”

Section: Targeting Isgs or Other Antiviral Proteinsmentioning

confidence: 99%

Evasion strategies of porcine reproductive and respiratory syndrome virus

Chen

Qiao

et al. 2023

Front. Microbiol.

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During the co-evolution of viruses and their hosts, viruses have developed various strategies for overcoming host immunological defenses so that they can proliferate efficiently. Porcine reproductive and respiratory syndrome virus (PRRSV), a significant virus to the swine industry across the world, typically establishes prolonged infection via diverse and complicated mechanisms, which is one of the biggest obstacles for controlling the associated disease, porcine reproductive and respiratory syndrome (PRRS). In this review, we summarize the latest research on how PRRSV circumvents host antiviral responses from both the innate and adaptive immune systems and how this virus utilizes other evasion mechanisms, such as the manipulation of host apoptosis and microRNA. A thorough understanding of the exact mechanisms of PRRSV immune evasion will help with the development of novel antiviral strategies against PRRSV.

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“…In PRRSV-infected animals, the virus leads to persistent infection resulting in long viremia lasting for more than four weeks. During persistent infection, although pigs may show no clinical symptoms the virus is capable of maintaining replication in tonsils and lymph nodes for several months, keeping shedding in the environment ( 15 ).…”

mentioning

confidence: 99%

Editorial: Porcine reproductive and respiratory syndrome virus - animal virology, immunology, and pathogenesis

Guo

Liu

2023

Front. Immunol.

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Editorial on the Research TopicPorcine reproductive and respiratory syndrome virus -animal virology, immunology, and pathogenesis Porcine reproductive and respiratory syndrome (PRRS) is one of the most important pig diseases causing huge economic losses worldwide. The causative agent, PRRS virus (PRRSV), is an enveloped, single-stranded, positive-sense RNA virus which is classified into the genus Betaarterivirus, subfamily Variarterivirinae, family Arteriviridae along with equine arteritis virus (EAV), lactate dehydrogenase-elevating virus of mice (LDV), and simian hemorrhagic fever virus (SHFV). Its genome is about 15 kb in length and contains at least 11 open reading frames (ORFs) with 5´cap and 3´polyadenylated tail (1-3). The nonstructural proteins (nsp1-12), owning the functions of protease, replicase and regulation of host cell gene expression and responsible for the synthesis of viral RNA, are encoded by ORF1a and ORF1b which occupy approximately two-thirds of the genome (4). The structural proteins including glycoprotein 2 (GP2), GP3, GP4, GP5, envelope protein (E), matrix protein (M), and nucleocapsid protein (N), expressed by a series of subgenomic RNAs, are encoded by ORFs 2-7 at the 3´terminus of the genome (5). Due to the lack of proofreading ability of PRRSV RNA-dependent RNA polymerase (RdRp), the viral genome is highly susceptible to mutation and recombination, which causes the emergence of novel PRRSV isolates worldwide (6). At present, PRRSV can be divided into two species: PRRSV-1 (European genotype, Betaarterivirus suid 1) and PRRSV-2 (North American genotype; Betaarterivirus suid 2). Both species show high genetic diversity and share approximately 60% nucleotide sequence identity, and each one can be further divided into several clades, substrains or lineages. In China, the dominant strains are PRRSV-2 and the outbreaks of highly pathogenic variants lead to concerns in the pig industry (7). PRRSV infection causes severe reproductive failure in sows and respiratory disease in pigs of all ages, which often leads to secondary bacterial infections (such as Haemophilus parasuis and Streptococcus suis) with greater clinical manifestations and higher mortality (8).

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Porcine Reproductive and Respiratory Syndrome Virus Adapts Antiviral Innate Immunity via Manipulating MALT1

Abstract: PRRSV is a major swine pathogen, suppresses innate immunity, and causes persistent infection and coinfection with other pathogens. As a central immune mediator, MALT1 plays essential roles in regulating immunity and inflammation.

Cited by 18 publications

References 58 publications

Porcine Reproductive and Respiratory Syndrome Virus Modulates the Switch of Macrophage Polarization from M1 to M2 by Upregulating MoDC-Released sCD83

Porcine Reproductive and Respiratory Syndrome Virus Modulates the Switch of Macrophage Polarization from M1 to M2 by Upregulating MoDC-Released sCD83

Evasion strategies of porcine reproductive and respiratory syndrome virus

Editorial: Porcine reproductive and respiratory syndrome virus - animal virology, immunology, and pathogenesis

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