Species-specific effects of the hcf-1 gene on baculovirus virulence

The host cell-specific factor 1 gene (hcf-1) of the baculovirus Autographa californica nuclear polyhedrosis virus (AcMNPV) is required for the efficient replication and/or stability of reporter plasmids carrying an AcMNPV-derived origin of DNA replication in a cell-specific manner; hcf-1 is required for reporter plasmid replication or stability in TN-368 cells, a cell line derived from the cabbage looper Trichoplusia ni, but not in IPLB-SF-21 (SF-21) cells, a cell line derived from the fall armyworm Spodoptera frugiperda (A. Lu and L. K. Miller, J. Virol. 69:6265-6272, 1995). To further define the function of hcf-1, recombinant viruses with null mutations in hcf-1 were constructed in SF-21 cells and the phenotype of the mutants was determined in selected cell lines as well as in insect larvae. In S. frugiperda larvae and SF-21 cells, the phenotype of hcf-1 mutants was indistinguishable from that of wild-type AcMNPV. In T. ni larvae as well as T. ni-derived cell lines, hcf-1 mutants exhibited a mutant phenotype. In TN-368 cells, the replication of hcf-1 mutants was extremely impaired; the phenotype included a defect in viral DNA replication, late gene transcription, and virus production as well as a complete cessation of host and viral protein synthesis. In another cell line derived from T. ni, the BTI-TN5B1-4 cell line, the hcf-1 mutants exhibited a less severe phenotype. In T. ni larvae, the infectivity of the budded form of hcf-1 mutants was decreased significantly (50-fold), although no difference in the oral infectivity of the occluded form was observed. T. ni larvae infected with hcf-1 mutants by either oral or hemocoelic routes, however, died 20 to 30% more slowly than those infected with wild-type AcMNPV. These data indicate that there is a host-specific requirement for hcf-1 and that it exerts cell line-specific effects and possibly tissue-specific effects on the rate at which the virus replicates, thereby affecting the virulence of the virus in a species-specific manner.