THE MECHANISM OF VIRUS ATTACHMENT TO HOST CELLS
Authors: Theodore T. Puck, Alan Garen, Jewell Cline
Journal: The Journal of Experimental Medicine (1951)

T1 virus does not attach to its host cell, E. coli B, in distilled water. By the proper addition of salts the rate of attachment can be adjusted to any desired value up to the maximum limit set by the diffusion rate of the virus. Salts of Ca(++), Mg(++), Ba(++), and Mn(++) bring about a reaction rate representing 100 per cent collision efficiency in a concentration of 5 x 10(-4)M. Both greater and smaller concentrations depress the attachment velocity. Salts of Na(+), K(+), NH(4) (+), and Li(+) display a similar pattern but require a tenfold greater concentration than that of the previous group to produce the same effect. Moreover, the maximum velocity attainable in solutions containing only monovalent cations is only half that achieved by the divalent salts. The trivalent cations Al(3+), Cr(3+), Fe(3+) permanently inactivate the virus. Activation by Mg(++) of an inert mixture of virus and host cells in distilled water is so rapid as to be beyond the limit of the resolving time of the experimental procedure, which is 20 seconds. The temperature dependence curve of virus-cell adsorption exhibits a maximum at 37 degrees C. and falls to a value representing approximately 3 per cent collision efficiency at 1 degrees C. Identical curves are obtained in nutrient broth and in 10(-)M MgCl(2) solution. Bacteriophage can be quantitatively adsorbed on to glass filters. In a study of several viruses this attachment reaction was found to require the same cofactors-both organic, like ltryptophane, as well as inorganic-which each specific virus required for its attachment to its host cell. The suggestion is made that the attachment of viruses to these filters is a useful model for their attachment to host cells. Virus attachment to glass filters is reversible. Such adsorbed virus can be recovered almost quantitatively by washing the filter with a solution in which the attachment reaction does not occur. Virus attachment to host cells is similarly reversible at least in its primary step. Distilled water at 0 degrees C. can produce almost complete liberation of T2 virus from host cells infected in 0.02 M NaCl solution. Two significant differences between the behavior of glass filters and host cells toward T1 virus are: (a) an excess ion concentration fails to inhibit virus attachment to the glass as it does to the host cell; and (b) no decrease in efficiency of attachment to glass occurs at low temperatures. These facts suggest that the inhibiting action on the infective process of excess cations and low temperatures involves chemical groupings on the cell surface, rather than on the virus. There is no detectable attachment whatever of T1 virus to E. coli cells specifically resistant to it, though still susceptible to other viruses. This experiment indicates that the ion-controlled attachment forces here considered are involved in the host-virus specificity. This conclusion is strengthened by the fact that several different viruses with different host-cell specificities have different ionic requirements for cell attachment. All of these observations lend themselves to explanation by a mechanism which pictures an initial addition reaction of cations to specific sites on the surface of the virus in particular, and possibly also of the host cell. Two complementary electrostatic configurations are so produced which can unite in a reaction with a high biological specificity, which yet exhibits 100 per cent collision efficiency. An excess of ions may cover up some of the attachment sites and so inhibit the reaction. By this picture the specificity of virus-cell invasion depends upon the binding energies of sites on both bodies for various ions, and the distribution of these sites over the two surfaces. Possible relationships of such a process to other biological systems are discussed.