Pathological lesions and viral localization of influenza A (H5N1) virus in experimentally infected Chinese rhesus macaques: implications for pathogenesis and viral transmission.

Chinese rhesus macaques infected with influenza virus A/Tiger/Harbin/01/2002 (H5N1) developed acute interstitial pneumonia with diffuse alveolar damage. The results of virus isolation, reverse transcriptase polymerase chain reaction, immunohistochemistry, and in situ hybridization showed that the lung was the major target organ of the H5N1 virus infection. No virus was detected in the extrapulmonary organs. The results of immunohistochemistry and in situ hybridization also showed that pneumocytes and macrophages of the lower airway, not the ciliary epithelium of the trachea and bronchi, were the chief target cells in the lung tissue of the infected Chinese rhesus macaque. Our data indicate that the Chinese rhesus macaque is suitable as a new primate model for H5N1 virus research, especially for the study of H5N1 virus transmission. The predilection of the H5N1 virus to infect the lower airway suggests that the failure of the virus to attach to the ciliary epithelium of the trachea and bronchi may be a limiting factor in human-to-human transmissibility of the H5N1 virus.