Apoptosis and pathogenesis of avian influenza A (H5N1) virus in humans.

The pathogenesis of avian influenza A (H5N1) virus in humans has not been clearly elucidated. Apoptosis may also play an important role. We studied autopsy specimens from 2 patients who died of infection with this virus. Apoptosis was observed in alveolar epithelial cells, which is the major target cell type for the viral replication. Numerous apoptotic leukocytes were observed in the lung of a patient who died on day 6 of illness. Our data suggest that apoptosis may play a major role in the pathogenesis of influenza (H5N1) virus in humans by destroying alveolar epithelial cells. This pathogenesis causes pneumonia and destroys leukocytes, leading to leukopenia, which is a prominent clinical feature of influenza (H5N1) virus in humans. Whether observed apoptotic cells were a direct result of the viral replication or a consequence of an overactivation of the immune system requires further studies.

Influenza A H5N1 replication sites in humans.

Tissue tropism and pathogenesis of influenza A virus subtype H5N1 disease in humans is not well defined. In mammalian experimental models, H5N1 influenza is a disseminated disease. However, limited previous data from human autopsies have not shown evidence of virus dissemination beyond the lung. We investigated a patient with fatal H5N1 influenza. Viral RNA was detected by reverse transcription-polymerase chain reaction in lung, intestine, and spleen tissues, but positive-stranded viral RNA indicating virus replication was confined to the lung and intestine. Viral antigen was detected in pneumocytes by immunohistochemical tests. Tumor necrosis factor-? mRNA was seen in lung tissue. In contrast to disseminated infection documented in other mammals and birds, H5N1 viral replication in humans may be restricted to the lung and intestine, and the major site of H5N1 viral replication in the lung is the pneumocyte.