Study of infectious virus production from HPV18/16 capsid chimeras

Using the HPV18 genome as the backbone, we exchanged the HPV18 L2 or L1 genes with those of HPV16. The intertypical exchange of HPV18 L1 with the HPV16 L1 produced genomes that efficiently replicated and produced infectious virus. Genomes containing an intertypical exchange of HPV18 L2 for the HPV16 L2 failed to produce infectious virus in multiple independently derived cell lines. Using chimeric constructs of individual capsid proteins, we identified a type-specific domain at the N-terminus of the HPV18L1 capsid protein, which interferes with its ability to cooperate with the HPV16 L2 protein to form infectious viral particles. Deletion of this domain allows for the cooperation of the HPV18 L1 protein and HPV16 L2 protein and production of infectious progeny. In addition, cooperation of this N-terminal HPV18 L1 deletion mutant protein with the wild-type HPV18 L2 protein efficiently replicates infectious virus but changes occur in the viral structure.