Study of H7N9 in macaques shows widespread, sustained replication

H7N9 avian flu, which emerged in humans in China in the spring of 2013 and has since caused more than 450 cases, was found to replicate well in both the upper and lower respiratory tracts of cynomolgus macaques, a model for humans, and to show extended replication in the upper tract, indicating the possibility of prolonged shedding and transmissibility, say findings of a study today in mBio.

Macaques were used because they reflect human physiology and attachment patterns of H7N9, even better than ferrets do, the authors explain.

The researchers inoculated eight 5-year-old cynomolgus macaques via the ocular, oral, intranasal, and intratracheal routes with infectious doses of H7N9. The animals were checked twice daily for clinical signs. Signs of disease began 1 day postinoculation (dpi), and clinical disease peaked at 3 to 4 dpi.

Six of the eight animals had obvious respiratory signs, including increased respirations, abdominal breathing, and coughing; only one had nasal discharge and cough. The induced clinical disease was judged to be moderate.

Chest films showed interstitial infiltration, first in the lower right lung lobe and then spreading. Oropharyngeal swabs were positive by 1 dpi and remained so through 6 dpi. Not all nasal swabs were positive, nor were conjunctival swabs. Bronchoalveolar lavage showed H7N9 virus in the fluid of all animals at 1 dpi that continued through 6 pdi. The authors surmised that virus shedding occurred primarily through the throat.

Lung changes were similar but less severe histopathologically to those in infected humans and included diffuse alveolar damage, infiltration of polymorphonuclear cells, and other changes.

Viral titers in nasal turbinates, oronasopharynges, tracheas, bronchi, and lung tissue samples showed the H7N9 replicated well in both the upper and lower respiratory tracts. However, the titers in samples from tissue other than the lung were higher than those in the lungs, and they did not decrease from 3 dpi to 6 dpi, as did those of the lung samples. The authors say this indicates not only widespread but also sustained viral replication throughout the upper respiratory tract.

Although H7N9 caused mild to moderate disease in the macaques, the authors say it was more pathogenic than seasonal influenza A virus and most 2009 H1N1 isolates but not as pathogenic as the 1918 flu virus or H5N1 avian flu.

H7N9 in humans has tended to be more severe than that induced in macaques in this study. The authors say this may be due to underlying medical complications in infected patients.
Aug 12 mBio study




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