title: Intragenic and extragenic suppression of a mutation in herpes simplex virus 1 UL34 that affects both nuclear envelope targeting and membrane budding.
abstract: Late in infection herpesviruses move DNA-filled capsids from the nucleus to the cytoplasm by enveloping DNA-containing capsids at the inner nuclear membrane (INM) and deenveloping them at the outer nuclear membrane. This process requires two conserved herpesvirus proteins, pUL31 and pUL34. Interaction between pUL34 and pUL31 is essential for targeting both proteins to the nuclear envelope (NE), and sequences that mediate the targeting interaction have been mapped in both proteins. Here, we show that a mutation in the INM-targeting domain of pUL34 fails to support production of infectious virus or plaque formation. The mutation results in multiple defects, including impaired interaction between pUL34 and pUL31, poor NE targeting of pUL34, and misregulated, capsid-independent budding of the NE. The mutant defects in virus production, plaque formation, and pUL31 interaction can be suppressed by other mutations in the INM-targeting domain of pUL31 and by additional mutations in the pUL34 coding sequence.
authors: Department of Microbiology, University of Iowa, BSB 3-432, Iowa City, IA 52242, USA. richard-roller@uiowa.edu
authors: Richard J
authors: RJ
authors: Roller
authors: Alison C
authors: AC
authors: Haugo
authors: Nora J
authors: NJ
authors: Kopping
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002522:Chlorocebus aethiops; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000472:pathogenicity*; D009685:Nuclear Envelope / Q000378:metabolism / Q000821:virology*; D009687:Nuclear Proteins / Q000235:genetics; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D013489:Suppression, Genetic; D014709:Vero Cells; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism*; D057074:Virus Release
chemical_list: D009687:Nuclear Proteins; C108721:UL31 protein, Human herpesvirus 1; C403420:UL34 protein, Human herpesvirus 1; D014764:Viral Proteins