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    Pathogeneses of respiratory infections with virulent and attenuated vaccinia viruses

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    Authors
    Hayasaka, Daisuke
    Ennis, Francis A.
    Terajima, Masanori
    UMass Chan Affiliations
    Center for Infectious Disease and Vaccine Research
    Document Type
    Journal Article
    Publication Date
    2007-03-01
    Keywords
    Animals
    Atrophy
    Brain
    CD4-Positive T-Lymphocytes
    CD8-Positive T-Lymphocytes
    Cells, Cultured
    Disease Models, Animal
    Female
    Immune Tolerance
    Lung
    Lymphocyte Count
    Mice
    Mice, Inbred C57BL
    Nose
    Respiratory Tract Infections
    Thymus Gland
    Vaccinia
    Vaccinia virus
    Virulence
    Virus Replication
    Life Sciences
    Medicine and Health Sciences
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    Abstract
    BACKGROUND: Respiratory infection with the neurovirulent vaccinia virus (VV) strain Western Reserve (WR) results in an acute infection of the lung followed by dissemination of the virus to other organs and causes lethality in mice. The mechanisms of lethality are not well-understood. In this study, we analyzed virus replication and host immune responses after intranasal infection with lethal and non-lethal doses of VV using the WR strain and the less virulent Wyeth strain. RESULTS: The WR strain replicated more vigorously in the lung and in the brain than the Wyeth strain. There were, however, no differences between the virus titers in the brains of mice infected with the higher lethal dose and the lower non-lethal dose of WR strain, suggesting that the amount of virus replication in the brain is unlikely to be the sole determining factor of lethality. The WR strain grew better in primary mouse lung cells than the Wyeth strain. Lethal infection with WR strain was associated with a reduced number of lymphocytes and an altered phenotype of the T cells in the lung compared to non-lethal infections with the WR or Wyeth strains. Severe thymus atrophy with a reduction of CD4 and CD8 double positive T cells was also observed in the lethal infection. CONCLUSION: These results suggest that the lethality induced by intranasal infection with a high dose of the WR strain is caused by the higher replication of virus in lung cells and immune suppression during the early phase of the infection, resulting in uncontrolled virus replication in the lung.
    Source
    Virol J. 2007 Feb 27;4:22. Link to article on publisher's site
    DOI
    10.1186/1743-422X-4-22
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/38494
    PubMed ID
    17326843
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1186/1743-422X-4-22
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