Influenza A H5N1 replication sites in humans
Mongkol Uiprasertkul1, Pilaipan Puthavathana, Kantima Sangsiriwut
1Mahidol University, Bangkok, Thailand.
Abstract:
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.
Insights
Human H5N1 influenza replication may be limited to the lung and intestine, unlike disseminated disease in other mammals. This study investigated viral RNA and antigen presence in tissues from a fatal H5N1 case.
Area of Science:
- Virology
- Pathology
- Immunology
Background:
- The tissue tropism and pathogenesis of influenza A virus subtype H5N1 in humans remain poorly understood.
- While H5N1 influenza presents as a disseminated disease in mammalian models, human autopsy data have suggested limited dissemination beyond the lungs.
Observation:
- This investigation focused on a patient who succumbed to H5N1 influenza.
- Viral RNA was identified in lung, intestine, and spleen tissues using reverse transcription-polymerase chain reaction.
- Evidence of virus replication (positive-stranded viral RNA) was primarily observed in the lung and intestine, with viral antigen detected in lung pneumocytes.
Findings:
- H5N1 viral replication in humans appears to be restricted to the lung and intestine, contrasting with disseminated infections in other species.
- The primary site of H5N1 viral replication within the lung is identified as the pneumocyte.
- Tumor necrosis factor-alpha mRNA was detected in lung tissue, suggesting an inflammatory response.
Implications:
- These findings refine our understanding of H5N1 pathogenesis in humans, suggesting organ-specific viral replication.
- Identifying pneumocytes as a major replication site in the lung could inform targeted therapeutic strategies.
- Further research is warranted to elucidate the mechanisms driving H5N1 tropism and disease severity in humans.
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