An attenuated live vaccine based on highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) protects piglets against HP-PRRS

Tian, Zhen; An, Tongqing; Zhou, Yanjun; Peng, Jinmei; Hu, Shouping; Wei, Tianchao; Jiang, Yifeng; Xiao, Yan; Tong, Guangzhi

doi:10.1016/j.vetmic.2009.03.003

Cited by 133 publications

(108 citation statements)

References 13 publications

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“…The virulent PRRSV strain HuN4 (GenBank accession no. EF635006) and the attenuated vaccine strain HuN4-F112 were maintained and titrated in Marc-145 cells as described previously (Tian et al, 2009;Tong et al, 2007) and were stored at 280 uC.…”

Section: Methodsmentioning

confidence: 99%

“…Seven serum samples were collected from four pigs 21 days after intramuscular inoculation with attenuated PRRSV vaccine strain HuN4-F112 (Tian et al, 2009) and from three specific-pathogen-free (SPF) pig sera. ELISA showed that all four PRRSV HuN4-F112-immunized pigs produced PRRSV-specific antibodies; the three SPF pig sera had no PRRSV-specific antibodies (Table 1).…”

Section: Anti-prrsv Immune Serum Enhances Prrsv Infection In Porcine mentioning

confidence: 99%

“…PRRS has caused substantial economic losses to the swine industry worldwide. To control this disease, researchers have developed a number of vaccines (Christopher-Hennings et al, 1997;Dee & Joo, 1997;PlanaDurán et al, 1997;Tian et al, 2009). The immunological effect and progression of PRRS, however, are influenced by a variety of host factors, and one crucial factor is antibodydependent enhancement (ADE) of infection (Christianson et al, 1993;Yoon et al, 1996Yoon et al, , 1997.…”

Section: Introductionmentioning

confidence: 99%

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Involvement of CD16 in antibody-dependent enhancement of porcine reproductive and respiratory syndrome virus infection

Guo

et al. 2015

Journal of General Virology

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The immunological effect of porcine reproductive and respiratory syndrome disease virus (PRRSV) vaccines is thought to be influenced by a variety of host factors, in which antibodydependent enhancement (ADE) of infection is one crucial factor. Here, we assessed the mechanism of ADE of PRRSV infection. First, we found that subneutralizing serum could induce ADE of PRRSV infection in porcine alveolar macrophages (PAMs). Quantitative PCR, Western blotting and flow cytometry revealed that CD16 is the most abundant Fcc receptor (FccR) expressed on the surface of PAMs; thus, the role of CD16 in ADE of PRRSV infection was examined in PAMs. By using functional blocking antibodies, we demonstrated that CD16 is involved in enhanced virus production in PRRSV-antibody immune complex-infected PAMs. Because PAMs co-express different FccR isoforms, we evaluated the effects of CD16 in FccRnon-bearing cells by transfection. Using these engineered cells, we found that CD16 could specifically bind to the PRRSV-antibody immune complex and subsequently mediate internalization of the virus, resulting in the generation of progeny virus. We also showed that efficient expression of CD16 required association of the FcR c-chain. Together, our findings provide significant new insights into PRRSV infection, which can be enhanced by CD16-mediated PRRSV-antibody immune complexes. This CD16-mediated ADE may induce a shift in PRRSV tropism towards CD16-expressing cells, distributing virus to more organs during virus infection.

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Section: Methodsmentioning

confidence: 99%

Section: Anti-prrsv Immune Serum Enhances Prrsv Infection In Porcine mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Involvement of CD16 in antibody-dependent enhancement of porcine reproductive and respiratory syndrome virus infection

Guo

et al. 2015

Journal of General Virology

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“…The PRRSV HuN4 strain (GenBank accession number: EF635006, http://www.ncbi.nlm.nih.gov/nuccore/EF635006) was first isolated in 2006 and characterized by extensive amino acid mutations in GP5 protein and 30 aa deletions in Nsp2 compared with CH1a strain (52). HuN4-F112, a virulence-attenuated vaccine strain of HuN4, was obtained by passaging the HP-PRRSV HuN4 on Marc-145 cells (112th passage) (53). SDA2 (GenBank accession number: JX878379.1, http://www.ncbi.…”

Section: Cells and Virusesmentioning

confidence: 99%

DDX19A Senses Viral RNA and Mediates NLRP3-Dependent Inflammasome Activation

Liu

et al. 2015

The Journal of Immunology

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The NLRP3 inflammasome plays a major role in innate immune responses by activating caspase-1, resulting in secretion of IL-1β and inflammatory pathologic responses. Viral RNA can induce NLRP3 inflammasome activation. However, none of the components of NLRP3 inflammasome has the ability to bind viral RNA. Therefore, it had been proposed that there might have been some unidentified cytosolic RNA sensors that could bind viral RNA and NLRP3 to initiate NLRP3 inflammasome activation. In this study, DDX19A, a member of the DEAD/H-box protein family, was identified as a novel component of NLRP3 inflammasome using arterivirus infection as a model. We found that DDX19A interacted with viral RNA and NLRP3. Knockdown of DDX19A expression efficiently inhibited procaspase-1 cleavage and IL-1β secretion in porcine reproductive and respiration syndrome virus (PRRSV)–infected or PRRSV RNA-stimulated primary porcine alveolar macrophages. Overall, DDX19A was identified as a novel cytosolic RNA sensor that bridged PRRSV RNA and NLRP3 to activate NLRP3 inflammasome.

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“…Several live attenuated North American-lineage PRRSV vaccines, such as Ingelvac1 ATP, RespPRRS MLV, RespPRRS/ Repro1 ATP, and CH-1R, have been successfully employed in field [7], and induce higher protection rates than with inactivated vaccines. To respond to the recently emerged HP-PRRSV, new live attenuated vaccines were developed by passaging HP-PRRSV isolates in MARC-145 cell lines [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Construction and in vitro evaluation of a recombinant live attenuated PRRSV expressing GM-CSF

Zhou

Jiang

et al. 2014

Virology Journal

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Background: Porcine reproductive and respiratory syndrome virus (PRRSV) continues to be an important problem for the swine industry. Inactivated vaccines and modified-live virus vaccines are widely used in the field; however, the efficacy of these PRRSV vaccines is suboptimal due to poor immunogenicity. Granulocyte-macrophage colony stimulating factor (GM-CSF) has been extensively used as an effective genetic and protein adjuvant to enhance the efficiencies vaccines expressing tumor or pathogen antigens. The purpose of this study was to determine if GM-CSF could increase the efficiency of PRRSV vaccine. Methods: The GM-CSF gene was inserted in the HuN4-F112 vaccine strain by overlap PCR. The expression of GM-CSF by the recombinant virus was confirmed with methods of indirect immunofluorescent assay (IFA) and Western blotting. The stability of recombinant virus was assessed by cDNA sequence and IFA after 20 passages. To detect the biological activity of GM-CSF expressed by the recombinant virus, bone marrow-derived dendritic cells (BMDCs) were isolated and co-cultured with the recombinant virus or parental virus and the surface phenotypes of BMDCs were examined by flow cytometric analysis. The cytokines secreted by BMDCs infected with PRRSV, or treated with LPS, GM-CSF or medium alone were evaluated by ProcartaPlexTM Multiplex Immunoassays and qRT-PCR. Results: A novel modified-live PRRSV vaccine strain expressing GM-CSF (rHuN4-GM-CSF) was successfully constructed and rescued. The GM-CSF protein was stable expressed in recombinant virus-infected cells after 20 passages. Analysis of virus replication kinetics showed that the novel vaccine strain expressing GM-CSF had a similar replication rate as the parental virus. In vitro studies showed that infection of porcine BMDCs with rHuN4-GM-CSF resulted in increased surface expression of MHCI+, MHCII + and CD80/86+ that was dependent on virus expressed GM-CSF. The expression of representative cytokines was significantly up-regulated when BMDCs were incubated with the recombinant GM-CSF expressing virus.

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An attenuated live vaccine based on highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) protects piglets against HP-PRRS

Cited by 133 publications

References 13 publications

Involvement of CD16 in antibody-dependent enhancement of porcine reproductive and respiratory syndrome virus infection

Involvement of CD16 in antibody-dependent enhancement of porcine reproductive and respiratory syndrome virus infection

DDX19A Senses Viral RNA and Mediates NLRP3-Dependent Inflammasome Activation

Construction and in vitro evaluation of a recombinant live attenuated PRRSV expressing GM-CSF

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