A novel strain of cynomolgus macaque cytomegalovirus: implications for host-virus co-evolution

Russell, Justen; Marsh, Angie K.; Willer, David O.; Ambagala, Aruna; Dzamba, Misko; Chan, John; Pilon, Richard; Fournier, Jocelyn; Brudno, Michael; Antony, Joseph M.; Sandstrom, Paul; Evans, Ben; MacDonald, Kelly S.

doi:10.1186/s12864-016-2588-3

Cited by 10 publications

(12 citation statements)

References 48 publications

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“…While RhCMVs and CyCMVs are closely related to each other, they still clustered separately according to the host species. Our novel RhCMV isolates were grouped with the RhCMV laboratory strains 68–1 and 180.92, whereas all of our MCM CyCMV isolates were closely aligned with the recently published isolate CyCMV Mauritius [19] and demonstrated a close sequence relationship to CyCMV Ottawa, an isolate derived from a Filipino-origin CM [9]. Thus, we have successfully isolated seven novel RhCMV and MCM CyCMV from animals housed at ONPRC.…”

Section: Resultssupporting

confidence: 63%

“…Here, we have increased our understanding of RhCMV and CyCMV by isolating and sequencing three new RhCMV strains derived from Indian-origin rhesus macaques born and housed at the ONPRC, and four CyCMV isolates derived from cynomolgus macaques originally born on the island of Mauritius. Only two CyCMV strains had been described prior to our present analysis, one from a Filipino-origin and the other from a Mauritius-origin CM [9,19]. Unfortunately, neither strain was full-length and both carried deletions of their RL13 homologue and adjoining regions of the genome.…”

Section: Discussionmentioning

confidence: 99%

“…The first two sequences of cynomolgus macaque CMV (CyCMV) were recently published, and contain multiple elongations, truncations, and deletions compared to predicted full-length RhCMV genomes [9,18,19]. Unfortunately, CyCMV has yet to be cloned as a BAC, precluding manipulation of the CyCMV genome for study in CM.…”

Section: Introductionmentioning

confidence: 99%

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Cross-Species Rhesus Cytomegalovirus Infection of Cynomolgus Macaques

et al. 2016

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Cytomegaloviruses (CMV) are highly species-specific due to millennia of co-evolution and adaptation to their host, with no successful experimental cross-species infection in primates reported to date. Accordingly, full genome phylogenetic analysis of multiple new CMV field isolates derived from two closely related nonhuman primate species, Indian-origin rhesus macaques (RM) and Mauritian-origin cynomolgus macaques (MCM), revealed distinct and tight lineage clustering according to the species of origin, with MCM CMV isolates mirroring the limited genetic diversity of their primate host that underwent a population bottleneck 400 years ago. Despite the ability of Rhesus CMV (RhCMV) laboratory strain 68–1 to replicate efficiently in MCM fibroblasts and potently inhibit antigen presentation to MCM T cells in vitro, RhCMV 68–1 failed to productively infect MCM in vivo, even in the absence of host CD8+ T and NK cells. In contrast, RhCMV clone 68–1.2, genetically repaired to express the homologues of the HCMV anti-apoptosis gene UL36 and epithelial cell tropism genes UL128 and UL130 absent in 68–1, efficiently infected MCM as evidenced by the induction of transgene-specific T cells and virus shedding. Recombinant variants of RhCMV 68–1 and 68–1.2 revealed that expression of either UL36 or UL128 together with UL130 enabled productive MCM infection, indicating that multiple layers of cross-species restriction operate even between closely related hosts. Cumulatively, these results implicate cell tropism and evasion of apoptosis as critical determinants of CMV transmission across primate species barriers, and extend the macaque model of human CMV infection and immunology to MCM, a nonhuman primate species with uniquely simplified host immunogenetics.

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Section: Resultssupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

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Cross-Species Rhesus Cytomegalovirus Infection of Cynomolgus Macaques

et al. 2016

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“…In another study, the phylogenetic trees of primate cytomegaloviruses and their hosts' were compared, and primate cytomegalovirus genomes were also analysed. The obtained results demonstrated the coevolution of these viruses with their hosts (Russell et al 2016). Furthermore, the avian and reptilian HVs were clustered into the subfamily Alphaherpesvirinae, relating to the development of birds from reptilian progenitors (McGeoch and Gatherer 2005).…”

Section: Herpesvirusesmentioning

confidence: 67%

Virus–Host Coevolution with a Focus on Animal and Human DNA Viruses

et al. 2019

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Viruses have been infecting their host cells since the dawn of life, and this extremely long-term coevolution gave rise to some surprising consequences for the entire tree of life. It is hypothesised that viruses might have contributed to the formation of the first cellular life form, or that even the eukaryotic cell nucleus originates from an infection by a coated virus. The continuous struggle between viruses and their hosts to maintain at least a constant fitness level led to the development of an unceasing arms race, where weapons are often shuttled between the participants. In this literature review we try to give a short insight into some general consequences or traits of virus-host coevolution, and after this we zoom in to the viral clades of adenoviruses, herpesviruses, nucleo-cytoplasmic large DNA viruses, polyomaviruses and, finally, circoviruses.

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“…CMVs display remarkable species-specificity, which results from long-term co-evolution with and adaptation to their mammalian hosts [13,14]. Comparison of the HCMV genome with those of non human primate-infecting CMVs indicated that duplication and gene copy number variation of non-core genes were common during CMV evolution and probably contributed to host adaptation [1,10].…”

Section: Introductionmentioning

confidence: 99%

Past and ongoing adaptation of human cytomegalovirus to its host

et al. 2020

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Cytomegaloviruses (order Herpesvirales) display remarkable species-specificity as a result of long-term co-evolution with their mammalian hosts. Human cytomegalovirus (HCMV) is exquisitely adapted to our species and displays high genetic diversity. We leveraged information on inter-species divergence of primate-infecting cytomegaloviruses and intra-species diversity of clinical isolates to provide a genome-wide picture of HCMV adaptation across different time-frames. During adaptation to the human host, core viral genes were commonly targeted by positive selection. Functional characterization of adaptive mutations in the primase gene (UL70) indicated that selection favored amino acid replacements that decrease viral replication in human fibroblasts, suggesting evolution towards viral temperance. HCMV intra-species diversity was largely governed by immune system-driven selective pressure, with several adaptive variants located in antigenic domains. A significant excess of positively selected sites was also detected in the signal peptides (SPs) of viral proteins, indicating that, although they are removed from mature proteins, SPs can contribute to viral adaptation. Functional characterization of one of these SPs indicated that adaptive variants modulate the timing of cleavage by the signal peptidase and the dynamics of glycoprotein intracellular trafficking. We thus used evolutionary information to generate experimentally-testable hypotheses on the functional effect of HCMV genetic diversity and we define modulators of viral phenotypes.

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A novel strain of cynomolgus macaque cytomegalovirus: implications for host-virus co-evolution

Cited by 10 publications

References 48 publications

Cross-Species Rhesus Cytomegalovirus Infection of Cynomolgus Macaques

Cross-Species Rhesus Cytomegalovirus Infection of Cynomolgus Macaques

Virus–Host Coevolution with a Focus on Animal and Human DNA Viruses

Past and ongoing adaptation of human cytomegalovirus to its host

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