title: Bacterial artificial chromosome derived simian varicella virus is pathogenic in vivo.
abstract: BACKGROUND
  Varicella zoster virus (VZV) is a neurotropic alphaherpesvirus that infects humans and results in chickenpox and herpes zoster. A number of VZV genes remain functionally uncharacterized and since VZV is an obligate human pathogen, rigorous evaluation of VZV mutants in vivo remains challenging. Simian varicella virus (SVV) is homologous to VZV and SVV infection of rhesus macaques (RM) closely mimics VZV infection of humans. Recently the SVV genome was cloned as a bacterial artificial chromosome (BAC) and BAC-derived SVV displayed similar replication kinetics as wild-type (WT) SVV in vitro.
  
  
  METHODS
  RMs were infected with BAC-derived SVV or WT SVV at 4x10(5) PFU intrabronchially (N=8, 4 per group, sex and age matched). We collected whole blood (PBMC) and bronchoalveolar lavage (BAL) at various days post-infection (dpi) and sensory ganglia during latent infection (>84 dpi) at necropsy and compared disease progression, viral replication, immune response and the establishment of latency.
  
  
  RESULTS
  Viral replication kinetics and magnitude in bronchoalveolar lavage cells and whole blood as well as rash severity and duration were similar in RMs infected with SVV BAC or WT SVV. Moreover, SVV-specific B and T cell responses were comparable between BAC and WT-infected animals. Lastly, we measured viral DNA in sensory ganglia from both cohorts of infected RMs during latent infection.
  
  
  CONCLUSIONS
  SVV BAC is as pathogenic and immunogenic as WT SVV in vivo. Thus, the SVV BAC genetic system combined with the rhesus macaque animal model can further our understanding of viral ORFs important for VZV pathogenesis and the development of second-generation vaccines.
authors.affiliation: Vaccine and Gene Therapy Institute, Oregon National Primate Research Center, Beaverton, OR 97006, USA. messaoud@ucr.edu.
authors.forename: Christine
authors.initials: C
authors.lastname: Meyer
authors.forename: Jesse
authors.initials: J
authors.lastname: Dewane
authors.forename: Kristen
authors.initials: K
authors.lastname: Haberthur
authors.forename: Flora
authors.initials: F
authors.lastname: Engelmann
authors.forename: Nicole
authors.initials: N
authors.lastname: Arnold
authors.forename: Wayne
authors.initials: W
authors.lastname: Gray
authors.forename: Ilhem
authors.initials: I
authors.lastname: Messaoudi
mesh_terms: D000818:Animals; D001769:Blood / Q000821:virology; D001992:Bronchoalveolar Lavage Fluid / Q000821:virology; D002644:Chickenpox / Q000473:pathology* / Q000821:virology*; D022202:Chromosomes, Artificial, Bacterial; D004195:Disease Models, Animal; D017950:Ganglia, Sensory / Q000821:virology; D008253:Macaca mulatta; D018140:Varicellovirus / Q000235:genetics* / Q000472:pathogenicity*; D017735:Virus Latency