A mouse model of swine influenza virus H9N2 infection with acute lung injury
ABSTRACT BALB/c mice inoculated intranasally with A/swine/HeBei/012/2008/ (H9N2) virus (SIV), showing acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), were observed for morbidity (lung histopathology, lung coefficient, lung wet/dry weight (W/D) ratio, arterial blood gas characteristics and inflammatory cells in bronchial alveolar lavage fluid (BALF)) and mortality. The results showed that, (1) on days 1-4 post infection (p.i.), mice appeared depressed and showed ruffled fur, reduced food intake, weight loss and hypoxemia with a decreased arterial partial oxygen pressure and an increased partial carbon dioxide pressure. (2) From day 4 p.i., mice began to die and showed pulmonary edema, hemorrhage and inflammatory cells in the alveolar exudate. The lung coefficient and lung W/D ratio significantly increased. (3) On days 3-8 p.i., inflammatory cells, especially alveolar macrophages and polymorphonuclears (PMNs) in BALF significantly increased. (4) The mortality rate reached 62.5%. This study established a successful animal model of ALI induced by infection with H9N2 SIV which may help in further investigations of the pathogenesis of human ALI/ARDS induced by H9N2 SIV infection. Keywords: wine influenza virus; H9N2 subtype; acute lung injury; mouse.
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ABSTRACT: Several cases of humans infected with the H9N2 avian influenza virus (AIV) have been described since 1999; however, the infectivity and pathogenicity of H9N2 in humans is not well defined. A non-human primate model in rhesus macaques was developed to study H9N2 virus infections as a means of better understanding the pathogenesis and virulence of this virus, in addition to testing antiviral drugs. Rhesus macaques inoculated with H9N2 AIV presented with biphasic fever and viral pneumonia. H9N2 was recovered from nasal washes and pharyngeal samples up to days 7-9 postinfection, followed by an increase in HI (hemagglutination inhibition) antibody titers. Tissue tropism and immunohistochemistry indicated that H9N2 AIV replicated in the upper respiratory tract (turbinate, trachea, and bronchus) and in all lobes of the lung. Our data suggest that rhesus macaques are a suitable animal model to study H9N2 influenza virus infections, particularly in the context of viral evolution and pathogenicity.Archives of Virology 05/2013; DOI:10.1007/s00705-013-1721-8 · 2.28 Impact Factor
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ABSTRACT: The antioxidant N-acetyl-l-cysteine (NAC) had been shown to inhibit replication of seasonal human influenza A viruses. Here, the effects of NAC on H9N2 swine influenza virus-induced acute lung injury (ALI) were investigated in mice. BALB/c mice were inoculated intranasally with 107 50% tissue culture infective doses (TCID50) of A/swine/HeBei/012/2008/(H9N2) viruses with or without NAC treatments to induce ALI model. The result showed that pulmonary inflammation, pulmonary edema, MPO activity, total cells, neutrophils, macrophages, TNF-α, IL-6, IL-1β and CXCL-10 in BALF were attenuated by NAC. Moreover, our data showed that NAC significantly inhibited the levels of TLR4 protein and TLR4 mRNA in the lungs. Pharmacological inhibitors of TLR4 (E5564) exerted similar effects like those determined for NAC in H9N2 swine influenza virus-infected mice. These results suggest that antioxidants like NAC represent a potential additional treatment option that could be considered in the case of an influenza A virus pandemic.International Immunopharmacology 09/2014; 22(1):1–8. DOI:10.1016/j.intimp.2014.06.013 · 2.71 Impact Factor
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ABSTRACT: On 19 February 2013, the first patient infected with a novel influenza A H7N9 virus from an avian source showed symptoms of sickness. More than 349 laboratory-confirmed cases and 109 deaths have been reported in mainland China since then. Laboratory-confirmed, human-to-human H7N9 virus transmission has not been documented between individuals having close contact; however, this transmission route could not be excluded for three families. To control the spread of the avian influenza H7N9 virus, we must better understand its pathogenesis, transmissibility, and transmission routes in mammals. Studies have shown that this particular virus is transmitted by aerosols among ferrets.Virology Journal 11/2014; 11(1):185. DOI:10.1186/1743-422X-11-185 · 2.09 Impact Factor