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Simultaneous Infection With Porcine Reproductive and Respiratory Syndrome and Influenza Viruses Abrogates Clinical Protection Induced by Live Attenuated Porcine Reproductive and Respiratory Syndrome Vaccination.

ABSTRACT: The porcine respiratory disease complex (PRDC) is responsible for significant economic losses in the pig industry worldwide. Porcine reproductive and respiratory syndrome virus (PRRSV) and swine influenza virus are major viral contributors to PRDC. Vaccines are cost-effective measures for controlling PRRS, however, their efficacy in the context of co-infections has been poorly investigated. In this study, we aimed to determine the effect of PRRSV-2 and swine influenza H3N2 virus co-infection on the efficacy of PRRSV modified live virus (MLV) vaccination, which is widely used in the field. Following simultaneous challenge with contemporary PRRSV-2 and H3N2 field isolates, we found that the protective effect of PRRS MLV vaccination on clinical disease and pathology was abrogated, although viral load was unaffected and antibody responses were enhanced. In contrast, co-infection in non-immunized animals reduced PRRSV-2 viremia and H3N2 virus load in the upper respiratory tract and potentiated T cell responses against both PRRSV-2 and H3N2 in the lung. Further analysis suggested that an upregulation of inhibitory cytokines gene expression in the lungs of vaccinated pigs may have influenced responses to H3N2 and PRRSV-2. These findings provide important insights into the effect of viral co-infections on PRRS vaccine efficacy that may help identify more effective vaccination strategies against PRDC in the field.

SUBMITTER: Chrun T

PROVIDER: S-EPMC8632230 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Simultaneous Infection With Porcine Reproductive and Respiratory Syndrome and Influenza Viruses Abrogates Clinical Protection Induced by Live Attenuated Porcine Reproductive and Respiratory Syndrome Vaccination.

Chrun Tiphany T Maze Emmanuel A EA Vatzia Eleni E Martini Veronica V Paudyal Basudev B Edmans Matthew D MD McNee Adam A Manjegowda Tanuja T Salguero Francisco J FJ Wanasen Nanchaya N Koonpaew Surapong S Graham Simon P SP Tchilian Elma E

Frontiers in immunology 20211111

The porcine respiratory disease complex (PRDC) is responsible for significant economic losses in the pig industry worldwide. Porcine reproductive and respiratory syndrome virus (PRRSV) and swine influenza virus are major viral contributors to PRDC. Vaccines are cost-effective measures for controlling PRRS, however, their efficacy in the context of co-infections has been poorly investigated. In this study, we aimed to determine the effect of PRRSV-2 and swine influenza H3N2 virus co-infection on ...[more]

PMID: 34858411

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Project description:There are no approved vaccines against the life-threatening Middle East respiratory syndrome coronavirus (MERS-CoV). Attenuated vaccines have proven their potential to induce strong and long-lasting immune responses. We have previously described that severe acute respiratory syndrome coronavirus (SARS-CoV) envelope (E) protein is a virulence factor. Based on this knowledge, a collection of mutants carrying partial deletions spanning the C-terminal domain of the E protein (rMERS-CoV-E*) has been generated using a reverse genetics system. One of these mutants, MERS-CoV-E*Δ2in, was attenuated and provided full protection in a challenge with virulent MERS-CoV after a single immunization dose. The MERS-CoV-E*Δ2in mutant was stable as it maintained its attenuation after 16 passages in cell cultures and has been selected as a promising vaccine candidate.IMPORTANCE The emergence of the new highly pathogenic human coronavirus SARS-CoV-2 that has already infected more than 80 million persons, killing nearly two million of them, clearly indicates the need to design efficient and safe vaccines protecting from these coronaviruses. Modern vaccines can be derived from virus-host interaction research directed to the identification of signaling pathways essential for virus replication and for virus-induced pathogenesis, in order to learn how to attenuate these viruses and design vaccines. Using a reverse genetics system developed in our laboratory, an infectious cDNA clone of MERS-CoV was engineered. Using this cDNA, we sequentially deleted several predicted and conserved motifs within the envelope (E) protein of MERS-CoV, previously associated with the presence of virulence factors. The in vitro and in vivo evaluation of these deletion mutants highlighted the relevance of predicted linear motifs in viral pathogenesis. Two of them, an Atg8 protein binding motif (Atg8-BM), and a forkhead-associated binding motif (FHA-BM), when deleted, rendered an attenuated virus that was evaluated as a vaccine candidate, leading to full protection against challenge with a lethal dose of MERS-CoV. This approach can be extended to the engineering of vaccines protecting against the new pandemic SARS-CoV-2.

Project description:Recombination is a significant factor driving the evolution of RNA viruses. The prevalence and variation of porcine reproductive and respiratory syndrome virus (PRRSV) in China have been increasing in complexity due to extensive interlineage recombination. When this recombination phenomenon occurs in live vaccine strains, it becomes increasingly difficult to prevent and control PRRSV. Reverse genetic manipulation to engineer a different transcriptional regulatory sequence (TRS) circuit introduces genetic traps into the viral genome that are lethal to recombinant RNA progeny viruses. In this study, major interlineage recombination patterns were identified between lineage 1 (L1) PRRSVs and lineage 8 (L8) PRRSVs in China, from 2019 to 2023. The recombinant mutant virus, vA-TRSall, was constructed and successfully rescued by rewiring the entire TRS circuit without changing the amino acid-coding sequence in the genome of the PRRSV live vaccine strain vHuN4-F112. The vA-TRSall, with a brand new TRS circuit, provided effective immune protection against the highly pathogenic L8 PRRSV (vHuN4) and epidemic NADC30-like L1 PRRSV (vZJqz21). Recombination analysis in vitro and in vivo showed that, compared with the vHuN4-F112 and vZJqz21 co-infection groups, the incidence rates of mutation breakpoints and template-switching recombination in the vA-TRSall and vZJqz21 co-infected groups were effectively reduced. The results have enriched our understanding of the critical role of TRS circuits in PRRSV recombination mechanisms and indicate a successful redesign that can endow PRRSV live vaccines with recombination-resistant capabilities.ImportancePorcine reproductive and respiratory syndrome viruses (PRRSVs) are genetically diverse, and this is due in part to their extensive recombination. Live vaccines are widely used to prevent and control PRRS in China. However, owing to the wide variety of live vaccines, non-standard use, and the wild viruses prevalent on pig farms, new strains, generated via RNA recombination, are continuously emerging. Vaccine strains are also involved in PRRSV recombination, which leads to the emergence of new variants and alterations in virulence and pathogenesis. A recombination-resistant genome was engineered by rewiring the entire transcriptional regulatory sequence (TRS) circuit of the live PRRSV vaccine strain. Theoretically, after clinical application, once the virus recombines with the genome of the epidemic strain, the base pairing between the two sets of TRS circuits should be disrupted, resulting in a fatal genetic trap for the generation of an RNA recombinant progeny virus. Therefore, the remodeled PRRSV TRS mutant generated in this study can serve as a recombination-resistant platform for the rational design of safe PRRS vaccines in the future.

Dataset Information

Simultaneous Infection With Porcine Reproductive and Respiratory Syndrome and Influenza Viruses Abrogates Clinical Protection Induced by Live Attenuated Porcine Reproductive and Respiratory Syndrome Vaccination.

Publications

Simultaneous Infection With Porcine Reproductive and Respiratory Syndrome and Influenza Viruses Abrogates Clinical Protection Induced by Live Attenuated Porcine Reproductive and Respiratory Syndrome Vaccination.

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