11 Adenovirus-SV40 Hybrids

Abstract

The adenovirus-SV40 hybrids are recombinants in which all or part of the adenoviral genome has become attached to part or all of the SV40 genome and is enclosed in the adenoviral capsid. They were originally isolated from stocks of human adenoviruses of types 1–5 and 7, which, for vaccine production, had been adapted to grow in rhesus monkey kidney (RhMK) cells (Hartley et al. 1956). Subsequently, hybrids of adenovirus type 12 and SV40 were isolated following the propagation of the two viruses together in African green monkey kidney (AGMK) cells (Schell et al. 1966).

In the mid-1950s, large stocks of human adenoviruses needed for vaccine production were obtained by repeatedly passaging the viruses in cultures of monkey cells (in which they grow extremely poorly) until adapted strains able to grow well in these cells emerged. However, the use of these human adenoviruses, adapted to grow in monkey cells for vaccination of military recruits, was abandoned after the virus stocks were found to be contaminated with SV40, a virus later shown to be virtually ubiquitous in rhesus monkeys and in kidney cell cultures derived from them (Sweet and Hilleman 1960). The persistence of SV40 in strains adapted to grow in monkey cells was not accidental, but was the result of strong selection pressures because adenoviral growth in monkey cells is greatly enhanced by coinfection with SV40 (Rabson et al. 1964) (see Chapter 9). At first, attempts were made to rid the adenoviral strains of SV40 by the addition of SV40-specific...