The Rivers ‘revived’ strain of vaccinia virus (), a population of virus particles produced in chorioallantoic membrane of eggs, is shown to be physically heterogeneous. Some cloned subpopulations isolated on RK cells interfere and others complement each other in mixed infection. Some are physically different, as shown by sedimentation velocity spectra, but none produce plaques on L cells. Yet pulse-inoculation (by centrifuging) at an input multiplicity of 20 virus particles per L cell produces progeny that make more plaques on L cells than on the RK cells from which they were selected. High multiplicity is essential to this process and the frequency of emerging L virus particles may be increased up to 400-fold if the recipient L cells are starved prior to inoculation. One cloned LRK virus, isolated from these progeny, is suppressed in plaque formation by antiserum to the original virus but it no longer produces the characteristic necrotic lesions in rabbit skin.

The sudden emergence of these large numbers of host-range variants in the absence of a mutagenic agent is similar in some respects to ‘symmetrical host-controlled modification’ observed with certain bacterial viruses.


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