Analysis of pseudorabies and herpes simplex virus recombinants simultaneously lacking the pUL17 and pUL25 components of the C-capsid specific component.

Homologs of the UL17 and UL25 gene products of herpes simplex virus 1 (HSV-1) are conserved throughout the Herpesviridae and essential for virus replication. However, their exact function is still unknown. Although both proteins form a complex on DNA-containing C-capsids defects observed in the absence of either protein differ. Absence of pUL17 from HSV-1 or the related alphaherpesvirus pseudorabies virus (PrV) precludes cleavage and packaging of newly replicated viral DNA, whereas in the absence of pUL25 genomic DNA is encapsidated but nuclear egress of capsids to the cytosol is abolished. HSV-1 pUL25 partially complemented the defect in a PrV UL25 deletion mutant indicating overlapping functions. However, reciprocal complementation did not ensue, and the present study demonstrates that UL17-deleted HSV-1 or PrV mutants are also not rescued by heterologous pUL17. To analyze whether simultaneous substitution of both complex partners may allow or increase trans-complementation we generated rabbit kidney cell lines co-expressing either PrV or HSV-1 pUL17 and pUL25, and respective HSV-1 and PrV double deletion mutants. Whereas the defects of both double mutants were trans-complemented by cell lines co-expressing the homologous complex partners, productive replication was not restored by heterologous pUL17 and pUL25. Thus, the protein complexes of PrV and HSV-1 either possess distinct functions, or require interactions with other viral proteins which are impaired in a heterologous context.