Inactivation and morphological changes of avian influenza virus by copper ions

The infectivity of the H9N2 virus to MDCK cells was time-dependently inhibited by Cu(2+) at concentrations of 2.5-250 mu M. In 25 mu M Cu(2+) solution, the virus titer decreased by approximately 3 and 4 log within 3 and 6 h, respectively. Compared to Cu(2+), Zn(2+) was much less effective in virus inactivation. The H9N2 virus hemagglutinin activity was not affected by 2.5-250 mu M Cu(2+). The H9N2 virus neuraminidase (NA) activity was drastically reduced by 25 mM Cu(2+), marginally reduced by 250 mu M Cu(2+), and not affected by 25 mu M Cu(2+). Thus, we found that copper ions suppress the infectivity of influenza virus at lower concentrations at which neither NA nor hemagglutination inhibition occurs. Electron microscopic analysis revealed morphological abnormalities of the Cu(2+)-treated H9N2 virus. Additional studies should be undertaken to clarify the mechanism underlying the antiviral effect of copper ions on influenza virus.