Bacterial artificial chromosome derived simian varicella virus is pathogenic in vivo
1 Vaccine and Gene Therapy Institute, Oregon National Primate Research Center, Beaverton, OR 97006, USA
2 Molecular Microbiology and Immunology Department, Oregon National Primate Research Center, Beaverton, OR 97006, USA
3 Division of Pathobiology and Immunology, Oregon National Primate Research Center, Beaverton, OR 97006, USA
4 Division of Biomedical Sciences, University of California-Riverside, Riverside, CA 92508, USA
5 Department of Microbiology and Immunology, University of Arkansas, Little Rock, AK 72205, USA
6 School of Medicine, University of California-Riverside, 900 University Avenue, Riverside, CA 92521, USA
Virology Journal 2013, 10:278 doi:10.1186/1743-422X-10-278Published: 8 September 2013
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.
RMs were infected with BAC-derived SVV or WT SVV at 4x105 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.
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.
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.