In vitro host range of Autographa californica nucleopolyhedrovirus recombinants lacking functional p35, iap1 or iap2

We have examined the host range in different insect cell lines of Autograph a californica nucleopolyhedrovirus (AcMNPV) recombinants lacking p35, iap1 or iap2. These genes encode, or are predicted to encode, anti-apoptotic pro teins. Abrogation of p35 reduced the ability of AcMNPV to replicate in perm issive cell lines derived from Spodoptera frugiperda insects by inducing ap optosis, In semi-permissive cell lines, such as Lymantria dispar and Spodop tera littoralis cells, we observed cytopathic effects after infection with AcMNPV but little virus production. Infection of these cells by AcMNPV lack ing p35 resulted in apoptosis. However, p35-deficient viruses were still ab le to replicate normally in Trichoplusia ni, Mamestra brassicae and Panolis flammea cell lines. Disruption of AcMNPV iap1 and iap2 was found not to af fect virus replication in any of the cell lines, It was also possible to di srupt both iap1 and iap2 in the same vi rus without loss of infectivity. A virus without iap1 and p35 demonstrated identical growth characteristics an d host range to a virus lacking p35. We conclude that in cells which respon d to AcMNPV infection by initiating programmed cell death, the p35 gene pro duct alone is sufficient to inhibit apoptosis. Removal of iap1 or iap2 has no effect on virus replication, even in cell lines which do not undergo apo ptosis in response to AcMNPV infection. Our results with two semi-permissiv e cell lines further indicate that whilst p35 is important in blocking bloc k apoptosis, other factors are involved in restricting AcMNPV replication w ithin these cells.