Immunogenic and antigenic analysis of recombinant NSP1 and NSP11 of PRRS virus

Contreras‐Luna, María Josefina; Segura‐Velázquez, René; Cervantes‐Torres, Jacquelynne; Alonso-Morales, Rogelio Alejandro; Ramírez‐Martínez, Luis Alfonso; Ayón‐Núñez, Dolores Adriana; Bobes, Raúl J.; Sánchez‐Betancourt, José Ivan

doi:10.1002/vms3.699

Cited by 4 publications

(3 citation statements)

References 38 publications

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“…PRRSV nsp11 is a well-established multifunctional protein known for its endoribonuclease and deubiquitinating activities [42,43], and it plays a crucial role in virus replication, making it a crucial component in the PRRSV lifecycle [44,45]. Further studies have displayed that nsp11 functions as a potent antagonist of the IFN response, employing various mechanisms to suppress IFN production.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…The other recombinant protein is NLNsp10L11, which consists of ORF7 plus NSP 10 and NSP11. It is well established that nonstructural proteins (NSPs) are the first viral proteins to be produced in cells infected by PRRSV [ 44 ]. Following our previous study, we examined the expression of CD163 in PAMs and the capacity for PAM repolarization by A3 and A4.…”

Section: Discussionmentioning

confidence: 99%

Toll-like Receptor-Mediated Immunomodulation of Th1-Type Response Stimulated by Recombinant Antigen of Type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV-2)

Wahyuningtyas

Chung

et al. 2023

Viruses

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PRRSV infects CD163-positive macrophages and skews their polarization toward an M2 phenotype, followed by T-cell inactivation. In our previous study, we found that recombinant protein A1 antigen derived from PRRSV-2 was a potential vaccine or adjuvant for immunization against PRRSV-2 infection due to its ability to repolarize macrophages into M1 subtype, thereby reducing CD163 expression for viral entry and promoting immunomodulation for Th1-type responses, except for stimulating Toll-like receptor (TLR) activation. The aim of our current study was to evaluate the effects of another two recombinant antigens, A3 (ORF6L5) and A4 (NLNsp10L11), for their ability to trigger innate immune responses including TLR activation. We isolated pulmonary alveolar macrophages (PAMs) from 8- to 12-week-old specific pathogen free (SPF) piglets and stimulated them with PRRSV (0.01 MOI and 0.05 MOI) or antigens. We also investigated the T-cell differentiation by immunological synapse activation of PAMs and CD4+ T-cells in the cocultured system. To confirm the infection of PRRSV in PAMs, we checked the expression of TLR3, 7, 8, and 9. Our results showed that the expression of TLR3, 7, and 9 were significantly upregulated in PAMs by A3 antigen induction, similar to the extent of PRRSV infection. Gene profile results showed that A3 repolarizes macrophages into the M1 subtype potently, in parallel with A1, as indicated by significant upregulation of proinflammatory genes (TNF-α, IL-6, IL-1β and IL-12). Upon immunological synapse activation, A3 potentially differentiated CD4 T cells into Th1 cells, determined by the expression of IL-12 and IFN-γ secretion. On the contrary, antigen A4 promoted regulatory T cell (T-reg) differentiation by significant upregulation of IL-10 expression. Finally, we concluded that the PRRSV-2 recombinant protein A3 provided better protection against PRRSV infection, suggested by its capability to reeducate immunosuppressive M2 macrophages into proinflammatory M1 cells. As M1 macrophages are prone to be functional antigen-presenting cells (APCs), they can call for TLR activation and Th1-type immune response within the immunological synapse.

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“…This NSP11 monoclonal antibody can be used as a primary antibody for indirect immunofluorescence experiments and can also be used for PRRSV diagnosis. In their study, Contreras-Luna et al [ 81 ] utilized recombinant proteins to generate hyperimmune sera and conducted serological assays to verify the presence of neutralizing antibodies. Their findings revealed that antibodies against PRRSV NSPs remained detectable up to 4 days after infection.…”

Section: Expression and Diagnosis Of Nsp11mentioning

confidence: 99%

Research Progress on NSP11 of Porcine Reproductive and Respiratory Syndrome Virus

Zheng

Zhang

Luo

et al. 2023

Veterinary Sciences

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Porcine reproductive and respiratory syndrome (PRRS) is a virulent infectious disease caused by the PRRS virus (PRRSV). The non-structural protein 11 (NSP11) of PRRSV is a nidovirus-specific endonuclease (NendoU), which displays uridine specificity and catalytic functions conserved throughout the entire NendoU family and exerts a wide range of biological effects. This review discusses the genetic evolution of NSP11, its effects on PRRSV replication and virulence, its interaction with other PRRSV and host proteins, its regulation of host immunity, the conserved characteristics of its enzyme activity (NendoU), and its diagnosis, providing an essential theoretical basis for in-depth studies of PRRSV pathogenesis and vaccine design.

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Immunogenic and antigenic analysis of recombinant NSP1 and NSP11 of PRRS virus

Cited by 4 publications

References 38 publications

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

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

Toll-like Receptor-Mediated Immunomodulation of Th1-Type Response Stimulated by Recombinant Antigen of Type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV-2)

Research Progress on NSP11 of Porcine Reproductive and Respiratory Syndrome Virus

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