title: The Us9 gene of bovine herpesvirus 1 (BHV-1) effectively complements a Us9-null strain of BHV-5 for anterograde transport, neurovirulence, and neuroinvasiveness in a rabbit model.
abstract: The alphaherpesvirus envelope protein Us9 is a type II viral membrane protein that is required for anterograde spread of bovine herpesvirus 5 (BHV-5) infection from the olfactory receptor neurons to the brain. In a rabbit seizure model, Us9-deleted BHV-5 failed to invade the central nervous system (CNS) following intranasal infection. However, when injected directly into the olfactory bulb, retrograde-spread infection from the olfactory bulb (OB) to the piriform cortex and other areas connected to the OB was not affected. In contrast to BHV-5, wild-type BHV-1 failed to invade the CNS following intranasal infection. In this study, we show that mature BHV-1 Us9 is a 30- to 32-kDa protein, whereas mature BHV-5 Us9 is an 18- to 20-kDa protein. In vitro, BHV-1 Us9 is expressed at 3 h postinfection (hpi), whereas BHV-5 Us9 is expressed at 6 hpi. Despite these differences, BHV-1 Us9 not only complemented for BHV-5 Us9 and rescued the anterograde-spread defect of the BHV-5 Us9-deleted virus but conferred increased neurovirulence and neuroinvasiveness in our rabbit seizure model. Rabbits infected with BHV-5 expressing BHV-1 Us9 showed severe neurological signs at 5 days postinfection, which was 1 to 2 days earlier than BHV-5 wild-type or Us9-reverted BHV-5 virus. The data underscore the importance of both Us9 genes for virion anterograde transport and neuroinvasiveness. However, Us9 is not the determinant of the differential neuropathogenesis of BHV-1 and BHV-5.
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas 66506, USA. chowdh@vet.k-state.edu
authors.forename: S I
authors.initials: SI
authors.lastname: Chowdhury
authors.forename: S
authors.initials: S
authors.lastname: Mahmood
authors.forename: J
authors.initials: J
authors.lastname: Simon
authors.forename: A
authors.initials: A
authors.lastname: Al-Mubarak
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000473:pathology / Q000821:virology; D017124:Conserved Sequence; D004195:Disease Models, Animal; D015967:Gene Expression Regulation, Viral; D005816:Genetic Complementation Test; D006566:Herpesviridae Infections / Q000473:pathology* / Q000821:virology; D007242:Herpesvirus 1, Bovine / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity*; D025881:Herpesvirus 5, Bovine / Q000235:genetics* / Q000472:pathogenicity; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009474:Neurons / Q000473:pathology / Q000821:virology*; D011499:Protein Processing, Post-Translational; D011817:Rabbits; D016415:Sequence Alignment; D013997:Time Factors; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D008562:Membrane Glycoproteins; D014764:Viral Proteins