title: Examining the species-specificity of rhesus macaque cytomegalovirus (RhCMV) in cynomolgus macaques.
abstract: Cytomegalovirus (CMV) is a highly species-specific virus that has co-evolved with its host over millions of years and thus restricting cross-species infection. To examine the extent to which host restriction may prevent cross-species research between closely related non-human primates, we evaluated experimental infection of cynomolgus macaques with a recombinant rhesus macaque-derived CMV (RhCMV-eGFP). Twelve cynomolgus macaques were randomly allocated to three groups: one experimental group (RhCMV-eGFP) and two control groups (UV-inactivated RhCMV-eGFP or media alone). The animals were given two subcutaneous inoculations at week 0 and week 8, and a subset of animals received an intravenous inoculation at week 23. No overt clinical or haematological changes were observed and PBMCs isolated from RhCMV-eGFP inoculated animals had comparable eGFP- and IE-1-specific cellular responses to the control animals. Following inoculation with RhCMV-eGFP, we were unable to detect evidence of infection in any blood or tissue samples up to 4 years post-inoculation, using sensitive viral co-culture, qPCR, and Western blot assays. Co-culture of urine and saliva samples demonstrated the presence of endogenous cynomolgus CMV (CyCMV) cytopathic effect, however no concomitant eGFP expression was observed. The absence of detectable RhCMV-eGFP suggests that the CyCMV-seropositive cynomolgus macaques were not productively infected with RhCMV-eGFP under these inoculation conditions. In a continued effort to develop CMV as a viral vector for an HIV/SIV vaccine, these studies demonstrate that CMV is highly restricted to its host species and can be highly affected by laboratory cell culture. Consideration of the differences between lab-adapted and primary viruses with respect to species range and cell tropism should be a priority in evaluating CMV as vaccine vector for HIV or other pathogens at the preclinical development stage.
authors.affiliation: Department of Immunology, University of Toronto, Toronto, ON, Canada.
authors.forename: Angie K
authors.initials: AK
authors.lastname: Marsh
authors.affiliation: Department of Microbiology, Mount Sinai Hospital, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Aruna P
authors.initials: AP
authors.lastname: Ambagala
authors.affiliation: Department of Immunology, University of Toronto, Toronto, ON, Canada.
authors.forename: Catia T
authors.initials: CT
authors.lastname: Perciani
authors.affiliation: Department of Immunology, University of Toronto, Toronto, ON, Canada.
authors.forename: Justen N Hoffman
authors.initials: JN
authors.lastname: Russell
authors.affiliation: Department of Microbiology, Mount Sinai Hospital, Toronto, ON, Canada.
authors.forename: Jacqueline K
authors.initials: JK
authors.lastname: Chan
authors.affiliation: National HIV & Retrovirology Laboratories, National HIV and Retrovirology Laboratories, Public Health Agency of Canada, Ottawa, ON, Canada.
authors.forename: Michelle
authors.initials: M
authors.lastname: Janes
authors.affiliation: Department of Microbiology, Mount Sinai Hospital, Toronto, ON, Canada.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Antony
authors.affiliation: National HIV & Retrovirology Laboratories, National HIV and Retrovirology Laboratories, Public Health Agency of Canada, Ottawa, ON, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Pilon
authors.affiliation: National HIV & Retrovirology Laboratories, National HIV and Retrovirology Laboratories, Public Health Agency of Canada, Ottawa, ON, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Sandstrom
authors.affiliation: Department of Microbiology, Mount Sinai Hospital, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: David O
authors.initials: DO
authors.lastname: Willer
authors.affiliation: Department of Immunology, University of Toronto, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Kelly S
authors.initials: KS
authors.lastname: MacDonald
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003587:Cytomegalovirus / Q000235:genetics*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D016130:Immunophenotyping; D008252:Macaca fascicularis / Q000821:virology*; D008297:Male; D012463:Saliva / Q000821:virology; D013045:Species Specificity; D014556:Urine / Q000821:virology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D014765:Viral Vaccines; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins
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