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      Viral Replication and Lung Lesions in BALB/c Mice Experimentally Inoculated with Avian Metapneumovirus Subgroup C Isolated from Chickens

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          Abstract

          Avian metapneumovirus (aMPV) emerged as an important respiratory pathogen causing acute respiratory tract infection in avian species. Here we used a chicken aMPV subgroup C (aMPV/C) isolate to inoculate experimentally BALB/c mice and found that the aMPV/C can efficiently replicate and persist in the lungs of mice for at least 21 days with a peak viral load at day 6 postinoculation. Lung pathological changes were characterized by increased inflammatory cells. Immunochemical assay showed the presence of viral antigens in the lungs and significant upregulation of pulmonary inflammatory cytokines and chemokines including MCP-1, MIP-1α, RANTES, IL-1β, IFN-γ, and TNF-α were detected following inoculation. These results indicate for the first time that chicken aMPV/C may replicate in the lung of mice. Whether aMPV/C has potential as zoonotic pathogen, further investigation will be required.

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          Most cited references25

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          Virological features and clinical manifestations associated with human metapneumovirus: a new paramyxovirus responsible for acute respiratory-tract infections in all age groups.

          The virological features and clinical findings associated with the new human metapneumovirus (HMPV) were examined retrospectively in Canadian patients hospitalized for various respiratory conditions since 1993. Thirty-eight previously unidentified respiratory viruses isolated from rhesus monkey kindey (LLC-MK2) cells were found to be positive for HMPV by reverse-transcription polymerase chain reaction, and those strains clustered in 2 phylogenetic groups. Children aged 65 years represented 35.1% and 45.9% of the HMPV-infected cases, respectively. In hospitalized children, the most frequent diagnoses were pneumonitis (66.7%) and bronchiolitis (58.3%), whereas bronchitis and/or bronchospasm (60%) and pneumonitis (40%) were most commonly seen in elderly subjects. Of the 15 patients with pneumonitis, 4 (26.7%) had immunosuppressive conditions and 6 (40%) were infants aged <15 months. These findings suggest that HMPV can be associated with severe lower-respiratory-tract infections in very young children, the elderly, and immunocompromised patients.
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            Analysis of the genomic sequence of a human metapneumovirus.

            We recently described the isolation of a novel paramyxovirus from children with respiratory tract disease in The Netherlands. Based on biological properties and limited sequence information the virus was provisionally classified as the first nonavian member of the Metapneumovirus genus and named human metapneumovirus (hMPV). This report describes the analysis of the sequences of all hMPV open reading frames (ORFs) and intergenic sequences as well as partial sequences of the genomic termini. The overall percentage of amino acid sequence identity between APV and hMPV N, P, M, F, M2-1, M2-2, and L ORFs was 56 to 88%. Some nucleotide sequence identity was also found between the noncoding regions of the APV and hMPV genomes. Although no discernible amino acid sequence identity was found between two of the ORFs of hMPV and ORFs of other paramyxoviruses, the amino acid content, hydrophilicity profiles, and location of these ORFs in the viral genome suggest that they represent SH and G proteins. The high percentage of sequence identity between APV and hMPV, their similar genomic organization (3'-N-P-M-F-M2-SH-G-L-5'), and phylogenetic analyses provide evidence for the proposed classification of hMPV as the first mammalian metapneumovirus.
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              Animal pneumoviruses: molecular genetics and pathogenesis.

              Pneumoviruses are single-stranded, negative-sense, nonsegmented RNA viruses of the family Paramyxoviridae, subfamily Pneumovirinae, and include pathogens that infect humans (respiratory syncytial virus and human metapneumovirus), domestic mammals (bovine, ovine, and caprine respiratory syncytial viruses), rodents (pneumonia virus of mice), and birds (avian metapneumovirus). Among the topics considered in this review are recent studies focused on the roles of the individual virus-encoded components in promoting virus replication as well as in altering and evading innate antiviral host defenses. Advances in the molecular technology of pneumoviruses and the emergence of recombinant pneumoviruses that are leading to improved virus-based vaccine formulations are also discussed. Since pneumovirus infection in natural hosts is associated with a profound inflammatory response that persists despite adequate antiviral therapy, we also review the recent experimental treatment strategies that have focused on combined antiviral, anti-inflammatory, and immunomodulatory approaches.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                17 March 2014
                : 9
                : 3
                : e92136
                Affiliations
                [1 ]Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, Beijing, People’s Republic of China
                [2 ]College of Veterinary Medicine, China Agricultural University, Beijing, People’s Republic of China
                [3 ]Molecular Virology Laboratory, QIMR Berghofer Medical Research Institute, Queensland, Australia
                French National Centre for Scientific Research, France
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: LW SSZ RPS JL. Performed the experiments: LW SSZ FJH JW XY CYZ SHL RQ ZXL FD. Analyzed the data: LW SSZ RPS JL. Contributed reagents/materials/analysis tools: SSZ FJH. Wrote the paper: TW JL.

                Article
                PONE-D-13-53387
                10.1371/journal.pone.0092136
                3956885
                24637582
                70812108-7360-41a0-90b8-d605c5e4172e
                Copyright @ 2014

                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.

                History
                : 18 December 2013
                : 18 February 2014
                Page count
                Pages: 7
                Funding
                This work was supported by a grant from China Agriculture Research System (CARS-42). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Microbiology
                Virology
                Viral Replication
                Veterinary Science
                Veterinary Diseases
                Veterinary Virology
                Veterinary Microbiology
                Zoology
                Avian Biology
                Medicine and Health Sciences
                Infectious Diseases
                Viral Diseases
                Human Metapneumovirus Infection
                Research and Analysis Methods
                Model Organisms
                Animal Models
                Mouse Models

                Uncategorized
                Uncategorized

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