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

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Title: Examining the species-specificity of rhesus macaque cytomegalovirus (RhCMV) in cynomolgus macaques.
Authors: 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.
Source: PloS one [PLoS One] 2015 Mar 30; Vol. 10 (3), pp. e0121339. Date of Electronic Publication: 2015 Mar 30 (Print Publication: 2015).
Publication Type: Evaluation Study; Journal Article; Research Support, Non-U.S. Gov't
Language: English
Journal Info: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
Imprint Name(s): Original Publication: San Francisco, CA : Public Library of Science
MeSH Terms: Cytomegalovirus/*genetics , Genetic Vectors/*genetics , Macaca fascicularis/*virology , Viral Vaccines/*pharmacology, Genetic Vectors/administration & dosage ; Green Fluorescent Proteins/genetics ; Green Fluorescent Proteins/metabolism ; Saliva/virology ; Urine/virology ; Viral Vaccines/administration & dosage ; Animals ; Blotting, Western ; Immunophenotyping ; Male ; Species Specificity
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.
Comments: Erratum in: PLoS One. 2015 May 14;10(5):e0128733. doi: 10.1371/journal.pone.0128733.. (PMID: 25973867)
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Grant Information: 107743 Canada Canadian Institutes of Health Research
Substance Nomenclature: 0 (Viral Vaccines)
0 (enhanced green fluorescent protein)
147336-22-9 (Green Fluorescent Proteins)
Entry Date(s): Date Created: 20150331 Date Completed: 20160321 Latest Revision: 20191210
Update Code: 20260130
PubMed Central ID: PMC4378995
DOI: 10.1371/journal.pone.0121339
PMID: 25822981
Database: MEDLINE
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  Label: Title
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  Data: Examining the species-specificity of rhesus macaque cytomegalovirus (RhCMV) in cynomolgus macaques.
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  Data: <searchLink fieldCode="AU" term="%22Marsh+AK%22">Marsh AK</searchLink>; Department of Immunology, University of Toronto, Toronto, ON, Canada.<br /><searchLink fieldCode="AU" term="%22Ambagala+AP%22">Ambagala AP</searchLink>; Department of Microbiology, Mount Sinai Hospital, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada.<br /><searchLink fieldCode="AU" term="%22Perciani+CT%22">Perciani CT</searchLink>; Department of Immunology, University of Toronto, Toronto, ON, Canada.<br /><searchLink fieldCode="AU" term="%22Russell+JN%22">Russell JN</searchLink>; Department of Immunology, University of Toronto, Toronto, ON, Canada.<br /><searchLink fieldCode="AU" term="%22Chan+JK%22">Chan JK</searchLink>; Department of Microbiology, Mount Sinai Hospital, Toronto, ON, Canada.<br /><searchLink fieldCode="AU" term="%22Janes+M%22">Janes M</searchLink>; National HIV & Retrovirology Laboratories, National HIV and Retrovirology Laboratories, Public Health Agency of Canada, Ottawa, ON, Canada.<br /><searchLink fieldCode="AU" term="%22Antony+JM%22">Antony JM</searchLink>; Department of Microbiology, Mount Sinai Hospital, Toronto, ON, Canada.<br /><searchLink fieldCode="AU" term="%22Pilon+R%22">Pilon R</searchLink>; National HIV & Retrovirology Laboratories, National HIV and Retrovirology Laboratories, Public Health Agency of Canada, Ottawa, ON, Canada.<br /><searchLink fieldCode="AU" term="%22Sandstrom+P%22">Sandstrom P</searchLink>; National HIV & Retrovirology Laboratories, National HIV and Retrovirology Laboratories, Public Health Agency of Canada, Ottawa, ON, Canada.<br /><searchLink fieldCode="AU" term="%22Willer+DO%22">Willer DO</searchLink>; Department of Microbiology, Mount Sinai Hospital, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada.<br /><searchLink fieldCode="AU" term="%22MacDonald+KS%22">MacDonald KS</searchLink>; Department of Immunology, University of Toronto, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada.
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  Data: <searchLink fieldCode="JN" term="%22101285081%22">PloS one</searchLink> [PLoS One] 2015 Mar 30; Vol. 10 (3), pp. e0121339. <i>Date of Electronic Publication: </i>2015 Mar 30 (<i>Print Publication: </i>2015).
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  Data: Evaluation Study; Journal Article; Research Support, Non-U.S. Gov't
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  Data: <i>Original Publication</i>: San Francisco, CA : Public Library of Science
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  Data: <searchLink fieldCode="MM" term="%22Cytomegalovirus%22">Cytomegalovirus</searchLink>/<searchLink fieldCode="MM" term="%22Cytomegalovirus+genetics%22">*genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Genetic+Vectors%22">Genetic Vectors</searchLink>/<searchLink fieldCode="MM" term="%22Genetic+Vectors+genetics%22">*genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Macaca+fascicularis%22">Macaca fascicularis</searchLink>/<searchLink fieldCode="MM" term="%22Macaca+fascicularis+virology%22">*virology</searchLink> <br /><searchLink fieldCode="MM" term="%22Viral+Vaccines%22">Viral Vaccines</searchLink>/<searchLink fieldCode="MM" term="%22Viral+Vaccines+pharmacology%22">*pharmacology</searchLink><br /><searchLink fieldCode="MH" term="%22Genetic+Vectors%22">Genetic Vectors</searchLink>/<searchLink fieldCode="MH" term="%22Genetic+Vectors+administration+%26+dosage%22">administration & dosage</searchLink> ; <searchLink fieldCode="MH" term="%22Green+Fluorescent+Proteins%22">Green Fluorescent Proteins</searchLink>/<searchLink fieldCode="MH" term="%22Green+Fluorescent+Proteins+genetics%22">genetics</searchLink> ; <searchLink fieldCode="MH" term="%22Green+Fluorescent+Proteins%22">Green Fluorescent Proteins</searchLink>/<searchLink fieldCode="MH" term="%22Green+Fluorescent+Proteins+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Saliva%22">Saliva</searchLink>/<searchLink fieldCode="MH" term="%22Saliva+virology%22">virology</searchLink> ; <searchLink fieldCode="MH" term="%22Urine%22">Urine</searchLink>/<searchLink fieldCode="MH" term="%22Urine+virology%22">virology</searchLink> ; <searchLink fieldCode="MH" term="%22Viral+Vaccines%22">Viral Vaccines</searchLink>/<searchLink fieldCode="MH" term="%22Viral+Vaccines+administration+%26+dosage%22">administration & dosage</searchLink> ; <searchLink fieldCode="MH" term="%22Animals%22">Animals</searchLink> ; <searchLink fieldCode="MH" term="%22Blotting%2C+Western%22">Blotting, Western</searchLink> ; <searchLink fieldCode="MH" term="%22Immunophenotyping%22">Immunophenotyping</searchLink> ; <searchLink fieldCode="MH" term="%22Male%22">Male</searchLink> ; <searchLink fieldCode="MH" term="%22Species+Specificity%22">Species Specificity</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: 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.
– Name: Comment
  Label: Comments
  Group: Commnt
  Data: Erratum in: PLoS One. 2015 May 14;10(5):e0128733. doi: 10.1371/journal.pone.0128733.. (PMID: <searchLink fieldCode="PM" term="%2225973867%22">25973867)</searchLink>
– Name: Ref
  Label: References
  Group: RefInfo
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              Text: 2015 Mar 30
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