Facilitated detection of adventitious agents using genetically engineered cell lines

Proposals to expand the number and types of cellular substrates used in the production of live attenuated vaccines, especially to include those of tumour origin, have raised concerns about the current capacity to detect adventitious agents that may be present in vaccine stocks. Detection of unknown agents is especially difficult because the culture systems used may not be optimal. We hypothesize that failure to grow certain viruses in culture may be the result of the cellular suicide mechanism, known as apoptosis, killing virus-infected cells before the virus can effectively replicate and spread. Our earlier work with an HIV-1 culture system which overexpresses the cellular anti-apoptotic gene, bcl-2, demonstrated that interfering with the apoptotic programme could facilitate HIV-1 expression and accelerate the kinetics of an acute spreading HIV-1 infection. These findings may have implications for improving cell culture detection systems to screen for potentially harmful infectious agents in current and developmental vaccine substrates. In this paper, we briefly review earlier work and discuss future studies aimed at manipulating the cellular apoptotic programme to facilitate the replication of adventitious and transforming viral agents in vitro.