title: The UL4 protein of equine herpesvirus 1 is not essential for replication or pathogenesis and inhibits gene expression controlled by viral and heterologous promoters.
abstract: Defective interfering particles (DIP) of equine herpesvirus 1 (EHV-1) inhibit standard virus replication and mediate persistent infection. The DIP genome is comprised of only three genes: UL3, UL4, and a hybrid gene composed of portions of the IR4 (EICP22) and UL5 (EICP27) genes. The hybrid gene is important for DIP interference, but the function(s) of the UL3 and UL4 genes are unknown. Here, we show that UL4 is an early gene activated solely by the immediate early protein. The UL4 protein (UL4P) was detected at 4hours post-infection, was localized throughout the nucleus and cytoplasm, and was not present in purified virions. EHV-1 lacking UL4P expression was infectious and displayed cell tropism and pathogenic properties in the mouse model similar to those of parental and revertant viruses. Reporter assays demonstrated that the UL4P has a broad inhibitory function, suggesting a potential role in establishing and/or maintaining DIP-mediated persistent infection.
authors.affiliation: Center for Molecular and Tumor Virology, Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130-3932, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Charvat
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Breitenbach
authors.forename: ByungChul
authors.initials: B
authors.lastname: Ahn
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: O'Callaghan
mesh_terms: D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000737:chemistry; D005786:Gene Expression Regulation; D004861:Herpesvirus 1, Equid / Q000472:pathogenicity* / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D011401:Promoter Regions, Genetic; D011817:Rabbits; D014764:Viral Proteins / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D014764:Viral Proteins; C076117:UL4 protein, Equine herpesvirus 1