BIOLOGICAL PROPERTIES OF A HEMAGGLUTININ MUTANT OF INFLUENZA-VIRUS SELECTED BY HOST-CELLS

Chick embryo fibroblast (CEF)-grown stocks of the WSN strain of influenza A (HINI) contain 2 variants which were designated F and C for fuzzy and clear plaque morphology on Madin-Darby bovine kidney (MDBK) cells. During growth in MDBK cells plaque-isolated F virus was completely replaced by C virus. The parental (F) and the mutant (C) viruses contain hemagglutinins which differ in their ability to bind to host cells. The host cells from which the purified viruses are obtained affect their binding properties. Thus, as compared to MDBK-grown F virus (FBK), MDBK-grown C virus (CBK) produced high amounts of mRNA and high virus yields in MDBK cells. CBK had greater affinity for SA.alpha.2,3Gal and SA.alpha.2,6Gal linkages on derivatized human erythrocytes than did FBK, independent of whether neuraminidase was present on the virions. CBK was also resistant to components of calf serum which inhibited FBK hemagglutination at 37.degree. C. As compared to FBK, CBK had increased ability to bind to both MDBK cells and CEF at 37.degree. C in the presence or absence of an inhibitor of neuraminidase. When cells with virus bound at 0.degree. C were transferred to 37.degree. C, CBK remained cell associated, whereas .apprx. 80% of FBK dissociated from both cells. Thus, mutation from F to C increased the ability of the virus to associate with MDBK cell receptors. Studies carried out with F and C viruses from both cells indicated that the expression of the mutation depended in part on the host cells in which the virus was grown and in part on the cells used to measure the binding properties. A model relating these observations to selection of HA variants in nature is presented.