title: Partial functional complementation of a pseudorabies virus UL25 deletion mutant by herpes simplex virus type 1 pUL25 indicates overlapping functions of alphaherpesvirus pUL25 proteins.
abstract: Homologs of the UL25 gene product of herpes simplex virus 1 (HSV-1) are highly conserved among the Herpesviridae. However, their exact function during viral replication is unknown. Current evidence suggests that in the alphaherpesvirus pseudorabies virus (PrV) the capsid-associated pUL25 plays a role in primary envelopment of DNA-containing mature capsids at the inner nuclear membrane. In the absence of pUL25, capsids were found in close association with the inner nuclear membrane, but nuclear egress was not observed (B. G. Klupp, H. Granzow, G. M. Keil, and T. C. Mettenleiter, J. Virol. 80:6235-6246, 2006). In contrast, HSV-1 pUL25 has been assigned a role in stable packaging of viral genomes (N. Stow, J. Virol. 75:10755-10765, 2001). Despite these apparently divergent functions, we wanted to assess whether the high sequence homology translates into functional homology. Therefore, we first analyzed a newly constructed HSV-1 UL25 deletion mutant in our assay system and observed a similar phenotype as in PrV. In the nuclei of infected cells, numerous electron-dense C capsids were detected, whereas primary envelopment of these capsids did not ensue. In agreement with results from PrV, vesicles were observed in the perinuclear space. Since these data indicated functional homology, we analyzed the ability of pUL25 of HSV-1 to complement a PrV UL25 deletion mutant and vice versa. Whereas a HSV-1 pUL25-expressing cell line partially complemented the pUL25 defect in PrV, reciprocal complementation of a HSV-1 UL25 deletion mutant by PrV pUL25 was not observed. Thus, our data demonstrate overlapping, although not identical functions of these two conserved herpesvirus proteins, and point to a conserved functional role in herpes virion formation.
authors.affiliation: Friedrich-Loeffler-Institut, Institute of Molecular Biology, Südufer 10, 17493 Greifswald-Insel Riems, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Kuhn
authors.forename: Tobias
authors.initials: T
authors.lastname: Leege
authors.forename: Barbara G
authors.initials: BG
authors.lastname: Klupp
authors.forename: Harald
authors.initials: H
authors.lastname: Granzow
authors.forename: Walter
authors.initials: W
authors.lastname: Fuchs
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Mettenleiter
mesh_terms: D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000648:ultrastructure / Q000821:virology; D002522:Chlorocebus aethiops; D017353:Gene Deletion; D005814:Genes, Viral; D018259:Herpesvirus 1, Human / Q000378:metabolism* / Q000648:ultrastructure; D011558:Herpesvirus 1, Suid / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D011817:Rabbits; D014162:Transfection; D014709:Vero Cells; D010948:Viral Plaque Assay; D015678:Viral Structural Proteins / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D014771:Virion / Q000648:ultrastructure
chemical_list: D015678:Viral Structural Proteins