Publications (4)11.93 Total impact
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Article: Porcine reproductive and respiratory syndrome virus: Genetic diversity of recent British isolates.
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ABSTRACT: Porcine reproductive and respiratory syndrome (PRRS) continues to be a significant problem for European pig producers, contributing to porcine respiratory disease complex, neonatal piglet mortality, infertility and occasional abortion storms. PRRS virus (PRRSV), a member of the arterivirus family with two defined major genotypes, has been shown to be quite genetically diverse. In the present study, genetic analysis of multiple gene regions of over 100 viruses isolated in Britain between 2003 and 2007 revealed that the diversity of British strains is now far greater than during the early 1990s. All isolates belong to genotype 1 (European). While some recent isolates are still very similar to early isolates, a wide range of more diverse viruses is now also circulating. Interestingly, some isolates were found to be very similar to a modified-live vaccine strain, and it is suggested that use of the vaccine has affected the evolution pattern of PRRS virus strains in Britain. Evidence of deletions in one viral gene, ORF3, and of genome recombination was also seen. A molecular clock model using the ORF7 sequences estimates the rate of substitution as 3.8×10(-3) per site per year, thereby dating the most recent common ancestor of all British viruses to 1991, coincident with the first outbreak of disease. Our findings therefore have implications for both the diagnostic and prophylactic methods currently being used, which are discussed.Veterinary Microbiology 11/2012; · 3.33 Impact Factor -
Article: Porcine reproductive and respiratory syndrome virus: antigenic and molecular diversity of British isolates and implications for diagnosis.
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ABSTRACT: Porcine reproductive and respiratory syndrome (PRRS) is an endemic disease of pigs, caused by PRRS virus, a member of the Arteriviridae family. First seen in Britain in 1991, the disease continues to be a significant economic and welfare problem for pig producers. To date, only PRRSV genotype 1 has been found in Britain. At the genetic level, a considerable increase has been reported in the diversity of PRRS viruses isolated in Britain between 2003 and 2007, versus the early 1990 s. In this study, the diversity has been shown to extend to the antigenic level too, with potential consequences for diagnostic methods. Antigenic diversity was assessed using a panel of twelve monoclonal antibodies, only one of which reacted with all isolates tested. Nine diverse viruses were compared as potential antigens in immunoperoxidase monolayer assays, where each one produced quite different results for a common panel of sera. As a single virus is used in each diagnostic assay, results must therefore be interpreted cautiously. For a real-time RT-PCR assay, published oligonucleotide primer and probe sequences were evaluated against available genetic sequences of British and European viruses, and were re-designed where considerable mismatches were found. The multiplex assay incorporating these modified primers to detect genotype 1 and 2 PRRS viruses was then validated for use with diagnostic sera and tissues. As the increasing degree of diversity exhibited by British strains is mirrored in other countries, PRRSV will continue to provide an ongoing challenge to diagnosis at a global, as well as national level.Veterinary Microbiology 03/2012; 158(3-4):308-15. · 3.33 Impact Factor -
Article: Host inhibits replication of European porcine reproductive and respiratory syndrome virus in macrophages by altering differential regulation of type-I interferon transcriptional response.
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ABSTRACT: Porcine reproductive and respiratory syndrome (PRRS) is an infectious disease caused by a positive RNA strand arterivirus. PRRS virus (PRRSV) interacts primarily with lung macrophages. Little is known how the virus subverts the innate immune response to initiate its replication in alveolar macrophages. Large-scale transcriptional responses of macrophages with different levels of susceptibility to PRRSV infection were compared over 30 h of infection. This study demonstrates a rapid and intense host transcriptional remodelling during the early phase of the replication of the virus which correlates with transient repression of type-I interferon transcript as early as 8 h post-infection. These results support the suggestion from previous studies that host innate immune response inhibits replication of European porcine reproductive and respiratory syndrome virus in macrophages by altering differential regulation of type-I interferon transcriptional response.Immunogenetics 03/2011; 63(7):437-48. · 2.93 Impact Factor -
Article: Functional analysis of the porcine USP18 and its role during porcine arterivirus replication.
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ABSTRACT: Emerging evidence places deubiquitylation at the core of a multitude of regulatory processes, ranging from cell growth to innate immune response and health, such as cancer, degenerative and infectious diseases. Little is known about deubiquitylation in pig and arterivirus infection. This report provides information on the biochemical and functional role of the porcine USP18 during innate immune response to the porcine respiratory and reproductive syndrome virus (PRRSV). We have shown that UBP gene is the ortholog of the murine USP18 (Ubp43) gene and the human ubiquitin specific protease 18 (USP18) gene and encodes a biochemically functional de-ubiquitin enzyme which inhibits signalling pathways that lead to IFN-stimulating response element (ISRE) promotor regulation. Furthermore we have demonstrated that overexpression of the porcine USP18 leads to reduced replication and/or growth of PRRSV. Our data contrast with the conclusion of numerous reports demonstrating that USP18-deficient mice are highly resistant to viral and bacterial infections and to oncogenic transformation by BCR-ABL, and highlight USP18 as a potential target gene that promotes reduced replication of PRRSV.Gene 04/2009; 439(1-2):35-42. · 2.34 Impact Factor
