The Dual Origin of Noninfective Rous Sarcomas23

Abstract
Tumors were induced in chickens with either high or low doses of Bryan's high-titer strain of Rous sarcoma virus (RSV). The RSV stock contained Rous-associated virus (RAV) required for maturation of this strain of RSV. The ability of the tumor cells to produce RSV in vivo and in vitro was tested at various times after infection to determine the conditions favoring the production of noninfective tumors. All tumors induced with high doses of RSV yielded high concentrations of RSV during the first few days after appearance of the tumors. Subsequently, however, the virus yield per gram of tumor sharply decreased and reached zero about 3 weeks after infection. The decrease in virus yield was accompanied first by diminished growth and then regression of the tumors. The results indicated that the disappearance of RSV from tumors previously containing high concentrations of the virus and the regression of these tumors were due to an immunological reaction by the host. Tumors induced with low doses of RSV contained little or no RSV during the first few days after appearance of the tumors. Subsequently, the virus yield from most low-dose tumors increased, reached a maximum about 1 month after infection, and then declined. Early, low-dose tumor cells, which failed to produce RSV when grown in tissue culture, produced large amounts of RSV when RAV was added to the cultures. If an excess of RAV were inoculated into chickens along with a low dose of RSV, a much higher proportion of cells from the resulting tumors produced virus in tissue culture than if no excess of RAV had been added. It is concluded that many tumors induced with low doses of RSV contain no infectious RSV because of the limited opportunity for coinfection or superinfection of the tumor cells with the helper virus RAV.