Phenotypic variation in influenza virus reassortants with identical gene constellations.

To determine which gene segments of influenza A viruses are responsible for the property of tissue tropism, reassortants were produced between the avian influenza strain, A/Mal/NY/6750/78 [H2N2] (Mal/NY), and a human strain, A/Udorn/307/72 [H3N2] (Udorn). The avian strain replicates in the intestinal tract of ducks and the human strain does not. Eight reassortants were shown by hybridization analysis to have the same gene constellation, having received hemagglutinin gene segment 4 from Udorn and the remaining seven gene segments from Mal/NY. With one exception, all reassortants containing the Udorn HA were restricted in their ability to traverse the digestive tract of ducks and replicate therein. The exception, reassortant R2, replicated to high titers in the intestinal tract. The R2 virus was shown to possess a hemagglutinin molecule that was antigenically distinguishable from the Udorn parent with polyclonal and monoclonal antibodies. The virus was "nonavid" in reaction with antihemagglutinin antibodies and was phenotypically similar to avian influenza viruses. The results suggest that the R2 hemagglutinin has undergone mutation(s) altering tissue tropism and antigenic properties of the virus. These studies illustrate the importance of the hemagglutinin gene in determining tissue tropism and present an example of phenotypic variation in a virus population with the same gene constellation but do not exclude a requirement for other gene products.