Giuseppe
Emeritus
J Virol. 2009 Aug 19. [Epub ahead of print]
A single amino acid substitution in a polymerase protein of an H5N1 influenza virus is associated with systemic infection and impaired T cell activation in mice.
Fornek JL, Gillim-Ross L, Santos C, Carter V, Ward JM, Cheng LI, Proll S, Katze MG, Subbarao K. - Department of Microbiology, University of Washington, Box 358070, Seattle, WA 98195, USA; Laboratory of Infectious Diseases, NIAID, NIH, Bldg 33, Room 3E13C_1, 33 North Dr., MSC 3203, Bethesda, MD 20892, USA; Comparative Medicine Branch, NIAID, NIH, Rockville, MD 20852, USA.
Transmission of H5N1 influenza viruses from birds to humans poses a significant public health threat. A substitution of glutamic acid for lysine at position 627 of the PB2 protein of H5N1 viruses has been identified as a virulence determinant. We utilized the BALB/c mouse model of H5N1 infection to examine how this substitution affects virus-host interactions and leads to systemic infection. Mice infected with H5N1 viruses containing lysine at amino acid (aa) 627 in the PB2 protein exhibited increased severity of lesions in the lung parenchyma and the spleen, increased apoptosis in the lungs, and a decrease in oxygen saturation. Gene expression profiling revealed that T cell receptor activation was impaired at 2 days post-infection (dpi) in the lungs of mice infected with these viruses. The inflammatory response was highly activated in the lungs of mice infected with these viruses and was sustained at 4 dpi. In the spleen, immune-related processes including NK cell cytotoxicity and antigen presentation were highly activated by 2 dpi. These differences are not solely attributable to differences in viral replication in the lungs, but also to an inefficient immune response early in infection. The timing and magnitude of the immune response to highly pathogenic influenza viruses is critical in determining the outcome of infection. Disruption of these factors by a single aa substitution in a polymerase protein of an influenza virus is associated with severe disease and correlates with the spread of the virus to extrapulmonary sites.
PMID: 19692471 [PubMed - as supplied by publisher]
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A single amino acid substitution in a polymerase protein of an H5N1 influenza virus is associated with systemic infection and impaired T cell activation in mice.
Fornek JL, Gillim-Ross L, Santos C, Carter V, Ward JM, Cheng LI, Proll S, Katze MG, Subbarao K. - Department of Microbiology, University of Washington, Box 358070, Seattle, WA 98195, USA; Laboratory of Infectious Diseases, NIAID, NIH, Bldg 33, Room 3E13C_1, 33 North Dr., MSC 3203, Bethesda, MD 20892, USA; Comparative Medicine Branch, NIAID, NIH, Rockville, MD 20852, USA.
Transmission of H5N1 influenza viruses from birds to humans poses a significant public health threat. A substitution of glutamic acid for lysine at position 627 of the PB2 protein of H5N1 viruses has been identified as a virulence determinant. We utilized the BALB/c mouse model of H5N1 infection to examine how this substitution affects virus-host interactions and leads to systemic infection. Mice infected with H5N1 viruses containing lysine at amino acid (aa) 627 in the PB2 protein exhibited increased severity of lesions in the lung parenchyma and the spleen, increased apoptosis in the lungs, and a decrease in oxygen saturation. Gene expression profiling revealed that T cell receptor activation was impaired at 2 days post-infection (dpi) in the lungs of mice infected with these viruses. The inflammatory response was highly activated in the lungs of mice infected with these viruses and was sustained at 4 dpi. In the spleen, immune-related processes including NK cell cytotoxicity and antigen presentation were highly activated by 2 dpi. These differences are not solely attributable to differences in viral replication in the lungs, but also to an inefficient immune response early in infection. The timing and magnitude of the immune response to highly pathogenic influenza viruses is critical in determining the outcome of infection. Disruption of these factors by a single aa substitution in a polymerase protein of an influenza virus is associated with severe disease and correlates with the spread of the virus to extrapulmonary sites.
PMID: 19692471 [PubMed - as supplied by publisher]
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