Novel reassortant H7N9 viruses were associated with severe and fatal respiratory disease in three patients. (Funded by the National Basic Research Program of China and others.).
Most persons with confirmed H7N9 virus infection had severe lower respiratory tract illness, were epidemiologically unrelated, and had a history of recent exposure to poultry. However, limited, nonsustained human-to-human H7N9 virus transmission could not be ruled out in four families.
The potential for avian influenza H5N1 outbreaks has increased in recent years. Thus, it is paramount to develop novel strategies to alleviate death rates. Here we show that avian influenza A H5N1-infected patients exhibit markedly increased serum levels of angiotensin II. High serum levels of angiotensin II appear to be linked to the severity and lethality of infection, at least in some patients. In experimental mouse models, infection with highly pathogenic avian influenza A H5N1 virus results in downregulation of angiotensin-converting enzyme 2 (ACE2) expression in the lung and increased serum angiotensin II levels. Genetic inactivation of ACE2 causes severe lung injury in H5N1-challenged mice, confirming a role of ACE2 in H5N1-induced lung pathologies. Administration of recombinant human ACE2 ameliorates avian influenza H5N1 virus-induced lung injury in mice. Our data link H5N1 virus-induced acute lung failure to ACE2 and provide a potential treatment strategy to address future flu pandemics.
Human infection associated with a novel reassortant avian influenza H7N9 virus has recently been identified in China. A total of 132 confirmed cases and 39 deaths have been reported. Most patients presented with severe pneumonia and acute respiratory distress syndrome. Although the first epidemic has subsided, the presence of a natural reservoir and the disease severity highlight the need to evaluate its risk on human public health and to understand the possible pathogenesis mechanism. Here we show that the emerging H7N9 avian influenza virus poses a potentially high risk to humans. We discover that the H7N9 virus can bind to both avian-type (α2,3-linked sialic acid) and human-type (α2,6-linked sialic acid) receptors. It can invade epithelial cells in the human lower respiratory tract and type II pneumonocytes in alveoli, and replicated efficiently in ex vivo lung and trachea explant culture and several mammalian cell lines. In acute serum samples of H7N9-infected patients, increased levels of the chemokines and cytokines IP-10, MIG, MIP-1β, MCP-1, IL-6, IL-8 and IFN-α were detected. We note that the human population is naive to the H7N9 virus, and current seasonal vaccination could not provide protection.
Background
In China, 30 human cases of H5N1 virus infection have been identified to date. We conducted a retrospective case-control study to identify risk factors for H5N1 disease in China.
Methods
A questionnaire about potential H5N1 exposures was administered to 28 H5N1 cases and 134 randomly selected age, gender, and location matched controls or proxies. Conditional logistic regression analyses were performed.
Results
Before their illness, urban cases had visited wet poultry markets while rural cases had exposure to sick or dead backyard poultry. Independent H5N1 risk factors in multivariable analyses were direct contact with sick or dead poultry (OR 506.6; 95% CI 15.7–16319.6; p=0.0004), indirect exposure to sick or dead poultry (OR 56.9; 95% CI 4.3–745.6; p=0.002), and visiting a wet poultry market (OR 15.4; 95% CI 3.0–80.2; p=0.001).
Conclusions
To prevent human H5N1 cases in China, education to avoid direct or close exposures to sick or dead poultry should be increased, and interventions to prevent the spread of H5N1 at live poultry markets should be implemented.
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