title: Na, an autoproteolytic product of the herpes simplex virus type 1 protease, can functionally substitute for the assembly protein ICP35.
abstract: The herpes simplex virus type 1 (HSV-1) protease and its substrate, the assembly protein ICP35, are involved in virion maturation. Both proteins are encoded by a single open reading frame but are translated independently from 3'-coterminal mRNAs of different sizes and are in frame. The herpesvirus shell assembles around an internal scaffold which is subsequently lost during packaging of the viral genome. The scaffold is composed of ICP35, which is the major component, and autoproteolytically processed forms of the viral protease containing sequences common to ICP35 (Nb). In the baculovirus system, HSV-1 intact capsids can be formed in the presence of the protease or ICP35, indicating that the protease may substitute for ICP35 (Thomsen et al., J. Virol. 68:2442-2457, 1994). This is further supported by the fact that ICP35, in contrast to the protease, is not absolutely essential for viral growth. The processed intermediate of the protease analogous to ICP35 is the 388-amino-acid (aa) protein, Na, which is an N-terminal 59-aa extension of the 329-aa ICP35. To directly examine whether Na can functionally substitute for ICP35 during viral replication, we first constructed a mutant virus, Na delta35, in which 35 aa from the N terminus of Na were deleted. Phenotypic analysis of the mutant showed that this deletion had no effect on protease function. The function of Na was further examined by construction of a plasmid expressing Na alone and testing its ability to complement the growth of the mutant Prb virus in the absence of ICP35. Our results demonstrate that Na can functionally substitute for ICP35 during viral replication.
authors.affiliation: Department of Virology, Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492-7660, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Robertson
authors.forename: P J
authors.initials: PJ
authors.lastname: McCann
authors.forename: L
authors.initials: L
authors.lastname: Matusick-Kumar
authors.forename: V G
authors.initials: VG
authors.lastname: Preston
authors.forename: M
authors.initials: M
authors.lastname: Gao
mesh_terms: D010450:Endopeptidases / Q000235:genetics* / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C054582:ICP35 protein, Human herpesvirus 1; D014764:Viral Proteins; D010450:Endopeptidases