Examining the species-specificity of rhesus macaque cytomegalovirus (RhCMV) in cynomolgus macaques.

Autor:	Marsh AK; Department of Immunology, University of Toronto, Toronto, ON, Canada., Ambagala AP; Department of Microbiology, Mount Sinai Hospital, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada., Perciani CT; Department of Immunology, University of Toronto, Toronto, ON, Canada., Russell JN; Department of Immunology, University of Toronto, Toronto, ON, Canada., Chan JK; Department of Microbiology, Mount Sinai Hospital, Toronto, ON, Canada., Janes M; National HIV & Retrovirology Laboratories, National HIV and Retrovirology Laboratories, Public Health Agency of Canada, Ottawa, ON, Canada., Antony JM; Department of Microbiology, Mount Sinai Hospital, Toronto, ON, Canada., Pilon R; National HIV & Retrovirology Laboratories, National HIV and Retrovirology Laboratories, Public Health Agency of Canada, Ottawa, ON, Canada., Sandstrom P; National HIV & Retrovirology Laboratories, National HIV and Retrovirology Laboratories, Public Health Agency of Canada, Ottawa, ON, Canada., Willer DO; Department of Microbiology, Mount Sinai Hospital, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada., MacDonald KS; Department of Immunology, University of Toronto, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada.
Jazyk:	angličtina
Zdroj:	PloS one [PLoS One] 2015 Mar 30; Vol. 10 (3), pp. e0121339. Date of Electronic Publication: 2015 Mar 30 (Print Publication: 2015).
DOI:	10.1371/journal.pone.0121339
Abstrakt:	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.
Databáze:	MEDLINE
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