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      Emergence of Fatal PRRSV Variants: Unparalleled Outbreaks of Atypical PRRS in China and Molecular Dissection of the Unique Hallmark

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          Abstract

          Porcine reproductive and respiratory syndrome (PRRS) is a severe viral disease in pigs, causing great economic losses worldwide each year. The causative agent of the disease, PRRS virus (PRRSV), is a member of the family Arteriviridae. Here we report our investigation of the unparalleled large-scale outbreaks of an originally unknown, but so-called “high fever” disease in China in 2006 with the essence of PRRS, which spread to more than 10 provinces (autonomous cities or regions) and affected over 2,000,000 pigs with about 400,000 fatal cases. Different from the typical PRRS, numerous adult sows were also infected by the “high fever” disease. This atypical PRRS pandemic was initially identified as a hog cholera-like disease manifesting neurological symptoms (e.g., shivering), high fever (40–42°C), erythematous blanching rash, etc. Autopsies combined with immunological analyses clearly showed that multiple organs were infected by highly pathogenic PRRSVs with severe pathological changes observed. Whole-genome analysis of the isolated viruses revealed that these PRRSV isolates are grouped into Type II and are highly homologous to HB-1, a Chinese strain of PRRSV (96.5% nucleotide identity). More importantly, we observed a unique molecular hallmark in these viral isolates, namely a discontinuous deletion of 30 amino acids in nonstructural protein 2 (NSP2). Taken together, this is the first comprehensive report documenting the 2006 epidemic of atypical PRRS outbreak in China and identifying the 30 amino-acid deletion in NSP2, a novel determining factor for virulence which may be implicated in the high pathogenicity of PRRSV, and will stimulate further study by using the infectious cDNA clone technique.

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          Most cited references 55

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          Multiple sequence alignment with Clustal X.

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            Improving the accuracy of PSI-BLAST protein database searches with composition-based statistics and other refinements.

            PSI-BLAST is an iterative program to search a database for proteins with distant similarity to a query sequence. We investigated over a dozen modifications to the methods used in PSI-BLAST, with the goal of improving accuracy in finding true positive matches. To evaluate performance we used a set of 103 queries for which the true positives in yeast had been annotated by human experts, and a popular measure of retrieval accuracy (ROC) that can be normalized to take on values between 0 (worst) and 1 (best). The modifications we consider novel improve the ROC score from 0.758 +/- 0.005 to 0.895 +/- 0.003. This does not include the benefits from four modifications we included in the 'baseline' version, even though they were not implemented in PSI-BLAST version 2.0. The improvement in accuracy was confirmed on a small second test set. This test involved analyzing three protein families with curated lists of true positives from the non-redundant protein database. The modification that accounts for the majority of the improvement is the use, for each database sequence, of a position-specific scoring system tuned to that sequence's amino acid composition. The use of composition-based statistics is particularly beneficial for large-scale automated applications of PSI-BLAST.
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              Nidovirales: a new order comprising Coronaviridae and Arteriviridae.

               D Cavanagh (1996)
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS ONE
                plos
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2007
                13 June 2007
                : 2
                : 6
                Affiliations
                [1 ]China Animal Disease Control Center, Beijing, China
                [2 ]Center for Molecular Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
                [3 ]Graduate University, Chinese Academy of Sciences, Beijing, China
                [4 ]College of Veterinary Medicine, China Agricultural University, Beijing, China
                [5 ]China-Japan Joint Laboratory of Molecular Immunology and Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
                US Naval Medical Research Center Detachment/Centers for Disease Control, United States of America
                Author notes
                * To whom correspondence should be addressed. E-mail: tiankg@ 123456263.net (KT); gaof@ 123456im.ac.cn (GG)

                Conceived and designed the experiments: GG KT. Performed the experiments: YF YD MS PJ XY TZ ZC XC XT DL YZ XD MQ LH LK HX SW. Analyzed the data: GG YF KT XY TZ DL JY YK. Contributed reagents/materials/analysis tools: GG KT. Wrote the paper: GG YF KT XY TZ.

                Article
                07-PONE-RA-00584R3
                10.1371/journal.pone.0000526
                1885284
                17565379
                Tian et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                Page count
                Pages: 10
                Categories
                Research Article
                Virology/Emerging Viral Diseases
                Virology/Virulence Factors and Mechanisms

                Uncategorized

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