PMC:2700745 / 18403-21208 JSONTXT

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Mice\nThe mouse remains the primary model for evaluating the antiviral therapy of influenza pneumonia, due to the inexpensiveness of the animals and their caging and the general fidelity of the illness in mice to the human disease (Sidwell and Smee, 2004). In addition, many reagents are available to study the effects of virus replication and treatment on the mouse immune system. The laboratory mouse can be experimentally infected with both seasonal influenza A viruses and influenza B viruses, but this usually requires some adaptation by multiple lung passage. The adapted virus can then infect murine lung cells, probably as a result of amino acid changes in the surface hemagglutinins that enable it to bind to cell-surface alpha 2,3-linked sialic acid molecules (Ibricevic et al., 2006). A recent advance in influenza A modeling has been the finding that the reconstructed 1918 pandemic influenza virus is lethal for mice (Jeffery et al., 2001, Taubenberger, 2006).\nA number of parameters may be used to monitor influenza virus infection in mice, including change in body weight, decline in arterial oxygen saturation, increase in serum alpha-1-acid glycoprotein, mean time to death, and lung weight, viral titer and pathology scores (Sidwell and Smee, 2000). Disease manifestations often depend on the infectivity and challenge dose of the virus and (for seasonal influenza virus strains) how well the virus has adapted to the host. If a virus replicates in mice without causing apparent illness, the effects of therapy can be monitored using parameters such as lung viral titers, increase in lung weight and increase in 1-acid glycoprotein (1-AG), all of which increase in nonlethally infected mice (Ottolini et al., 2005, Sidwell and Smee, 2000).\nMost of the histopathological features of influenza viral pneumonia listed above are also seen in mice, but some signs and symptoms of human influenza are rarely observed. Mice do not show outward signs of fever and do not have increased rectal temperatures, nor is dyspnea, cyanosis or hemoptysis easily, if ever detected in mice infected with strains other than the H5N1 virus. However, as in humans, reduced blood oxygen saturation levels, a measure of lung function, can be measured in mice, and these levels are dramatically lower as pneumonia progresses and the mice approach death (Barnard et al., 2007). Weight loss is also a good marker of disease severity (Sidwell and Smee, 2000). The reader is referred to the following recent papers that show the utility of the seasonal influenza mouse model for evaluating vaccines (reviewed by van der Laan et al., 2008, Hagenaars et al., 2008, Hai et al., 2008) and antiviral drugs (Dimmock et al., 2008, Gilbert and McLeay, 2008, Reading et al., 2008, Smee et al., 2008, Wang et al., 2008)."}