Enhanced interferon production from chick embryo cells aged in in vitro.

The plaque-forming efficiency of Sindbis virus decreased as much as 1000-fold, and plaque size was diminished markedly, when tested on chick embryo cell monolayers aged in vitro. The plaquing efficiency and plaque size of Newcastle disease virus was unaffected. The reaction(s) associated with aging in vitro which lead to lowered plaquing efficiency are slowed considerably when cell monolayers are: (1) established in Simpson-Hirst medium rather than standard growth medium; (2) held at 31 degrees ; (3) given a regimen of daily medium changes; or (4) trypsinized and used as young secondary cultures. A loss in the average yield of virus per cell accompanies the loss in plaquing efficiency of Sindbis virus on aged monolayers. Adding actinomycin D to the aged cells at the time of infection eliminated completely the inhibition of Sindbis virus replication. Cells aged for 7 days in vitro were found to produce up to 32 times more interferon than cells 1-2 days old and were more sensitive to the action of interferon. The decrease in efficiency of Sindbis virus plaquing and yield in aged cells is accounted for by their development of an enhanced capacity to synthesize interferon upon appropriate stimulation. The process of contact inhibition and its concomitant regulation of macromolecular synthesis seems implicated in the aging phenomenon in that it may produce a generalized state of "enhanced derepressibility" in the cell.