The mechanism of immune dysregulation caused by porcine reproductive and respiratory syndrome virus (PRRSV)

Toman, M.; Štěpánová, Kateřina; Štěpánová, Hana; Levá, Lenka; Šinkorová, Jana; Moutelíková, Romana; Salát, Jiřı́; Šrůtková, Dagmar; Schwarzer, Martin; Sinkora, Simon; Skalníková, Helena Kupcová; Nechvátalová, Kateřina; Hudcovic, Tomáš; Hermanová, Petra; Pfeiferova, Sarka; Kratochvilova, Mirka; Kavanová, Lenka; Dusankova, Blanka; Šinkora, Marek

doi:10.1016/j.micinf.2023.105146

Cited by 4 publications

(13 citation statements)

References 49 publications

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“…PRRSV could evade host innate immunity, leading to a delayed response of NAs and immunosuppression [ 8 , 12 , 22 ]. PRRSV structural protein GP5 has a neutralizing epitope and plays an important role in the pathogenicity and immune evasion of PRRSV [ 16 , 20 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…Porcine reproductive and respiratory syndrome (PRRS) is a viral disease caused by PRRS virus (PRRSV) with serious reproductive disorders in sows and respiratory symptoms in piglets, leading to significant economic losses in the pig industry worldwide. Genetic diversity, immunosuppression, and the antibody-dependent enhancement (ADE) effect of PRRSV pose additional challenges for PRRS prevention and control [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ]. Although vaccination is the most effective method to prevent PRRSV infection, the efficacy of PRRSV vaccines remains unsatisfactory [ 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

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Mass Spectrometry-Based Proteomic Analysis of Potential Host Proteins Interacting with GP5 in PRRSV-Infected PAMs

Li,

Wang,

Zhang

et al. 2024

IJMS

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Porcine reproductive and respiratory syndrome virus (PRRSV) is a typical immunosuppressive virus causing a large economic impact on the swine industry. The structural protein GP5 of PRRSV plays a pivotal role in its pathogenicity and immune evasion. Virus–host interactions play a crucial part in viral replication and immune escape. Therefore, understanding the interactions between GP5 and host proteins are significant for porcine reproductive and respiratory syndrome (PRRS) control. However, the interaction network between GP5 and host proteins in primary porcine alveolar macrophages (PAMs) has not been reported. In this study, 709 GP5-interacting host proteins were identified in primary PAMs by immunoprecipitation coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Bioinformatics analysis revealed that these proteins were involved in multiple cellular processes, such as translation, protein transport, and protein stabilization. Subsequently, immunoprecipitation and immunofluorescence assay confirmed that GP5 could interact with antigen processing and presentation pathways related proteins. Finally, we found that GP5 may be a key protein that inhibits the antigen processing and presentation pathway during PRRSV infection. The novel host proteins identified in this study will be the candidates for studying the biological functions of GP5, which will provide new insights into PRRS prevention and vaccine development.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mass Spectrometry-Based Proteomic Analysis of Potential Host Proteins Interacting with GP5 in PRRSV-Infected PAMs

Li,

Wang,

Zhang

et al. 2024

IJMS

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“…The virus exhibits extensive genetic and antigenic diversity, leading to the emergence of numerous new strains and limiting the effectiveness of current vaccines. PRRSV infection is characterized by its ability to evade the host's innate immune response, resulting in delayed protective antibody production and cell-mediated immune responses, which contributes to the complexity of PRRS prevention and control [10,11]. Therefore, a deeper and more comprehensive understanding of PRRSV antagonizing the host antiviral response is critical for developing novel therapeutic strategies to combat this virus.…”

Section: Introductionmentioning

confidence: 99%

Innate Immune Evasion of PRRSV nsp11 through Degradation of the HDAC2 by Its Endoribonuclease Activity

Zhang,

Chen,

et al. 2024

Viruses

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Porcine reproductive and respiratory syndrome virus (PRRSV), a member of the Arteriviridae family, represents a persistent menace to the global pig industry, causing reproductive failure and respiratory disease in pigs. In this study, we delved into the role of histone deacetylases (HDAC2) during PRRSV infection. Our findings revealed that HDAC2 expression is downregulated upon PRRSV infection. Notably, suppressing HDAC2 activity through specific small interfering RNA led to an increase in virus production, whereas overexpressing HDAC2 effectively inhibited PRRSV replication by boosting the expression of IFN-regulated antiviral molecules. Furthermore, we identified the virus’s nonstructural protein 11 (nsp11) as a key player in reducing HDAC2 levels. Mutagenic analyses of PRRSV nsp11 revealed that its antagonistic effect on the antiviral activity of HDAC2 is dependent on its endonuclease activity. In summary, our research uncovered a novel immune evasion mechanism employed by PRRSV, providing crucial insights into the pathogenesis of this virus and guiding the development of innovative prevention strategies against PRRSV infection.

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“…Viruses are involved in many of these diseases, and new ones continue to emerge. In swine, an arterivirus called Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) infects the thymus, can cause thymic atrophy, alter thymocyte development and dysregulate T cell development (1). PRRSV is responsible for a pandemic, which is a very feared, frustrating, and costly infection for farmers.…”

Section: Introductionmentioning

confidence: 99%

“…Vaccination with MLV can stabilize the herd to some degree, but success is inconsistent, PRRSV frequently reappears, and cannot be eradicated. Given the etiology of PRRSV and our recent finding how PRRSV disorganizes neonatal thymic development and consequently humoral immune responses (1), it was important to determine if MLV behave differently than wild-type viruses, particularly in young animals. Indeed, previous results show that older animals that were not previously infected as piglets can produce effective VN antibodies (4-6), suggesting that this dysregulation does not occur in animals never exposed to the virus as neonates.…”

Section: Introductionmentioning

confidence: 99%

Modified live vaccine strains of porcine reproductive and respiratory syndrome virus cause immune system dysregulation similar to wild strains

Stepanova,

Toman,

Sinkorova

et al. 2024

Front. Immunol.

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IntroductionPorcine reproductive and respiratory syndrome virus (PRRSV) emerged about 30 years ago and continues to cause major economic losses in the pork industry. The lack of effective modified live vaccines (MLV) allows the pandemic to continue.Background and objectiveWe have previously shown that wild strains of PRRSV affect the nascent T cell repertoire in the thymus, deplete T cell clones recognizing viral epitopes essential for neutralization, while triggering a chronic, robust, but ineffective antibody response. Therefore, we hypothesized that the current MLV are inappropriate because they cause similar damage and fail to prevent viral-induced dysregulation of adaptive immunity. MethodsWe tested three MLV strains to demonstrate that all have a comparable negative effect on thymocytes in vitro. Further in vivo studies compared the development of T cells in the thymus, peripheral lymphocytes, and antibody production in young piglets. These three MLV strains were used in a mixture to determine whether at least some of them behave similarly to the wild virus type 1 or type 2. ResultsBoth the wild and MLV strains cause the same immune dysregulations. These include depletion of T-cell precursors, alteration of the TCR repertoire, necrobiosis at corticomedullary junctions, low body weight gain, decreased thymic cellularity, lack of virus-neutralizing antibodies, and production of non-neutralizing anti-PRRSV antibodies of different isotypes. Discussion and conclusionThe results may explain why the use of current MLV in young animals may be ineffective and why their use may be potentially dangerous. Therefore, alternative vaccines, such as subunit or mRNA vaccines or improved MLV, are needed to control the PRRSV pandemic.

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The mechanism of immune dysregulation caused by porcine reproductive and respiratory syndrome virus (PRRSV)

Cited by 4 publications

References 49 publications

Mass Spectrometry-Based Proteomic Analysis of Potential Host Proteins Interacting with GP5 in PRRSV-Infected PAMs

Mass Spectrometry-Based Proteomic Analysis of Potential Host Proteins Interacting with GP5 in PRRSV-Infected PAMs

Innate Immune Evasion of PRRSV nsp11 through Degradation of the HDAC2 by Its Endoribonuclease Activity

Modified live vaccine strains of porcine reproductive and respiratory syndrome virus cause immune system dysregulation similar to wild strains

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