Porcine Innate and Adaptative Immune Responses to Influenza and Coronavirus Infections

Charley, Bernard; Riffault, Sabine; Reeth, Kristien Van

doi:10.1196/annals.1373.014

Cited by 42 publications

(35 citation statements)

References 29 publications

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“…The innate immune response is critical for host defence against respiratory coronaviruses (CoVs) (Charley et al , 2006; Frieman et al , 2008; Thiel & Weber, 2008). Most CoVs are sensitive to the antiviral effects of virus-induced IFN-α/β.…”

Section: Introductionmentioning

confidence: 99%

“…Most CoVs are sensitive to the antiviral effects of virus-induced IFN-α/β. Specifically, the group 1 CoVs in the family Coronaviridae , order Nidovirales , PRCV and transmissible gastroenteritis virus (TGEV) are potent IFN-α inducers (Charley et al , 2006; Van Reeth et al , 1999; Zhang et al , 2008). The recently identified human CoV, severe acute respiratory syndrome coronavirus (SARS)-CoV, which belongs to subgroup 2b of the group 2 CoVs (Kuiken et al , 2003; Lau et al , 2005; Saif, 2004), also elicits type I interferons (IFNs), but it may also evade their antiviral activity (Frieman et al , 2008; Thiel & Weber, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Porcine reproductive and respiratory syndrome virus modifies innate immunity and alters disease outcome in pigs subsequently infected with porcine respiratory coronavirus: implications for respiratory viral co-infections

Jung

Renukaradhya

Alekseev

et al. 2009

Journal of General Virology

101

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The innate immune response is critical for host defence against respiratory coronaviruses (CoVs). This study demonstrated that an ongoing respiratory virus infection compromises innate immune responses and affects the pathogenesis of a respiratory CoV co-infection. An innate immunosuppressive respiratory virus infection was established by infecting weaned pigs with porcine reproductive and respiratory syndrome virus (PRRSV); 10 days later, the pigs were exposed to porcine respiratory coronavirus (PRCV). The PRRSV/PRCV dual-infected pigs had reduced weight gains, a higher incidence of fever and more severe pneumonia compared with either single infection. Significant suppression of innate immune responses [reduced alpha interferon (IFN-a) levels in the lungs and reduced blood natural killer cell cytotoxicity] by the ongoing PRRSV infection was observed in dual-infected pigs, which coincided with exacerbated pneumonia during early PRCV infection. The subsequent PRCV infection led to enhanced PRRSV replication in the lungs and a trend towards increased serum T-helper type 1 (Th1) (IFN-c) but decreased Th2 [interleukin (IL)-4] responses, further exacerbating PRRSV pneumonia. Following PRCV infection, more severe PRRSV-related pulmonary alveolar macrophage (PAM) apoptosis occurred, as determined by an in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay, suggesting increased PRRSV replication in PAMs. Collectively, these observations suggest interactive effects between PRCV and PRRSV via early innate (IFN-a) and later adaptive Th1 (IFN-c) and Th2 (IL-4) immune responses. These findings imply that an existing immunomodulating respiratory viral co-infection may be a contributing factor to more severe pneumonia in respiratory CoV disease. This study provides new insights into host-pathogen interactions related to co-infection by CoVs and other respiratory viruses.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Porcine reproductive and respiratory syndrome virus modifies innate immunity and alters disease outcome in pigs subsequently infected with porcine respiratory coronavirus: implications for respiratory viral co-infections

Jung

Renukaradhya

Alekseev

et al. 2009

Journal of General Virology

101

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“…11,14,54,55,59,126,148 Contradictory results from various studies on the interactions of components of the inflammatory response suggest that the severity of tissue damage is determined by the balance between proinflammatory and anti-inflammatory cytokine activity. An in-depth discussion of the complex multitude of molecules involved in the innate immune response to influenza virus infection is beyond the scope of this review, but an excellent review article on immunopathology has recently been published.…”

Section: Immunopathologymentioning

confidence: 99%

Influenza A Virus Infections in Swine

Janke

2013

Vet Pathol

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Influenza has been recognized as a respiratory disease in swine since its first appearance concurrent with the 1918 ''Spanish flu'' human pandemic. All influenza viruses of significance in swine are type A, subtype H1N1, H1N2, or H3N2 viruses. Influenza viruses infect epithelial cells lining the surface of the respiratory tract, inducing prominent necrotizing bronchitis and bronchiolitis and variable interstitial pneumonia. Cell death is due to direct virus infection and to insult directed by leukocytes and cytokines of the innate immune system. The most virulent viruses consistently express the following characteristics of infection: (1) higher or more prolonged virus replication, (2) excessive cytokine induction, and (3) replication in the lower respiratory tract. Nearly all the viral proteins contribute to virulence. Pigs are susceptible to infection with both human and avian viruses, which often results in gene reassortment between these viruses and endemic swine viruses. The receptors on the epithelial cells lining the respiratory tract are major determinants of infection by influenza viruses from other hosts. The polymerases, especially PB2, also influence cross-species infection. Methods of diagnosis and characterization of influenza viruses that infect swine have improved over the years, driven both by the availability of new technologies and by the necessity of keeping up with changes in the virus. Testing of oral fluids from pigs for virus and antibody is a recent development that allows efficient sampling of large numbers of animals.Keywords influenza virus, swine, pathogenesis, cytokines, apoptosis, virulence, cross-species infection, hemagglutinin, receptors, polymerases, diagnosisThe evolution and epidemiology of influenza A virus (IAV) infections in swine have been integrally tied to the segmented nature of the genome of the virus, which facilitates gene reassortment, and to the adaptability of these genes through mutation, which sometimes facilitates replication in a new host. 8,19,77,85,89 Influenza was first recognized as a respiratory disease entity in swine during the 1918 human Spanish flu pandemic. 67 The virus was not isolated until 1931, when nasal discharge from pigs was inoculated into ferrets and subsequently into embryonated chicken eggs. 129 In 1933, a similar virus was recovered from humans with this technique. 131 The viruses were essentially identical and served as the prototype for type A subtype H1N1 influenza viruses.All influenza viruses of significance that infect swine are type A viruses, defined by the highly conserved internal nucleoproteins and matrix proteins. Influenza A virus subtypes are based on the external hemagglutinin (HA) and neuraminidase (NA) proteins. The predominant viruses in swine populations in different parts of the world may have genes of different origin, even though the subtypes may be similar. 10,73,171 The original classic H1N1 swine influenza virus, which remained the predominant influenza virus in North American swine populations for nearl...

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“…Based on these findings, we hypothesized that PEDV PLP2 inhibits the IFN expression pathway through a similar mechanism. To test this hypothesis HEK293T cells were transfected with PEDV PLP2 or the corresponding catalytic mutants (C1729A, H1888A, D1901A) together with Flag-RIG-IN, the Nterminal helicase domain of RIG-I as its constitutively active mutant, or Flag-STING, and IFN-b-Luc or PRD(III-I)4-luc reporters; NL63 PLP2 was used as a positive control for IFN antagonist (Charley et al, 2006;Zeng et al, 2010). IFN-b and IRF3 promoter-driven luciferase activity was detected 24 h later.…”

Section: Pedv Plp2 Negatively Regulates Rig-i and Stingmediated Ifn-bmentioning

confidence: 99%

“…Accumulating evidence suggests that PEDV encodes a defensive mechanism(s) to evade the antiviral activities of IFN. PEDV suppresses production of type I IFN (IFN-a/b) in infected Vero cells and alveolar macrophages (Charley et al, 2006;Laude et al, 1993). Furthermore, PEDV diminishes IFN-a/b production induced by infection with transmissible gastroenteritis coronavirus (TGEV) or transfection with double-stranded RNA (dsRNA) (Albina et al, 1998;Miller et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

The papain-like protease of porcine epidemic diarrhea virus negatively regulates type I interferon pathway by acting as a viral deubiquitinase

Xing

Chen

et al. 2013

Journal of General Virology

146

170

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Porcine epidemic diarrhea virus (PEDV) is the cause of an economically important swine disease. Previous studies suggested that PEDV does not elicit a robust IFN response, but the mechanism(s) used to evade or block this innate immune response was not known. In this study, we found that PEDV infection blocked synthetic dsRNA-induced IFN-b production by interfering with the activation of interferon regulatory factor 3 (IRF3). We identified PEDV replicase encoded papain-like protease 2 (PLP2) as an IFN antagonist that depends on catalytic activity for its function. We show that levels of ubiquitinated proteins are reduced during PEDV infection and that PEDV PLP2 has deubiquitinase (DUB) activity that recognizes and processes both K-48 and K-63 linked polyubiquitin chains. Furthermore, we found that PEDV PLP2 strongly inhibits RIG-Iand STING-activated IFN expression and that PEDV PLP2 can be co-immunoprecipitated with and deubiquitinates RIG-I and STING, the key components of the signalling pathway for IFN expression. These results show that PEDV infection suppresses production of IFN-b and provides evidence indicating that the PEDV papain-like protease 2 acts as a viral DUB to interfere with the RIG-I-and STING-mediated signalling pathway.

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Porcine Innate and Adaptative Immune Responses to Influenza and Coronavirus Infections

Cited by 42 publications

References 29 publications

Porcine reproductive and respiratory syndrome virus modifies innate immunity and alters disease outcome in pigs subsequently infected with porcine respiratory coronavirus: implications for respiratory viral co-infections

Porcine reproductive and respiratory syndrome virus modifies innate immunity and alters disease outcome in pigs subsequently infected with porcine respiratory coronavirus: implications for respiratory viral co-infections

Influenza A Virus Infections in Swine

The papain-like protease of porcine epidemic diarrhea virus negatively regulates type I interferon pathway by acting as a viral deubiquitinase

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