Novel cytomegaloviruses in free-ranging and captive great apes: Phylogenetic evidence for bidirectional horizontal transmission

Research Group Emerging Zoonoses, Robert Koch-Institut, D-13353 Berlin, Germany.
Journal of General Virology (Impact Factor: 3.18). 07/2009; 90(Pt 10):2386-94. DOI: 10.1099/vir.0.011866-0
Source: PubMed


Wild great apes often suffer from diseases of unknown aetiology. This is among the causes of population declines. Because human cytomegalovirus (HCMV) is an important pathogen, especially in immunocompromised individuals, a search for cytomegaloviruses (CMVs) in deceased wild and captive chimpanzees, gorillas and orang-utans was performed. By using a degenerate PCR targeting four conserved genes (UL54-UL57), several distinct, previously unrecognized CMVs were found for each species. Sequences of up to 9 kb were determined for ten novel CMVs, located in the UL54-UL57 block. A phylogenetic tree was inferred for the ten novel CMVs, the previously characterized chimpanzee CMV, HCMV strains and Old World and New World monkey CMVs. The primate CMVs fell into four clades, containing New World monkey, Old World monkey, orang-utan and human CMVs, respectively, plus two clades that each contained both chimpanzee and gorilla isolates (termed CG1 and CG2). The tree loci of the first four clades mirrored those for their respective hosts in the primate tree, suggesting that these CMV lineages arose through cospeciation with host lineages. The CG1 and CG2 loci corresponded to those of the gorilla and chimpanzee hosts, respectively. This was interpreted as indicating that CG1 and CG2 represented CMV lineages that had arisen cospeciationally with the gorilla and chimpanzee lineages, respectively, with subsequent transfer within each clade between the host genera. Divergence dates were estimated and found to be consistent with overall cospeciational development of major primate CMV lineages. However, CMV transmission between chimpanzees and gorillas in both directions has also occurred.

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    • "We also note that this region is directly upstream of SLC23A1, a vitamin C transporter and PAIP2, a repressor of polyadenylate-binding protein PABP1. PAIP2 acts as part of innate defense against cytomegalovirus (CMV) (McKinney et al. 2013), which has been detected in wild gorilla populations (Leendertz et al. 2009). Another region identified (at P < 10 "
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    ABSTRACT: While population-level genomic sequence data have been gathered extensively for humans, similar data from our closest living relatives are just beginning to emerge. Examination of genomic variation within great apes offers many opportunities to increase our understanding of the forces that have differentially shaped the evolutionary history of hominid taxa. Here, we expand upon the work of the Great Ape Genome Project by analyzing medium to high coverage whole genome sequences from 14 western lowland gorillas (Gorilla gorilla gorilla), 2 eastern lowland gorillas (Gorilla beringei graueri), and a single Cross River individual (Gorilla gorilla diehli). We infer that the ancestors of western and eastern lowland gorillas diverged from a common ancestor ~261 thousand years ago (kya), and that the ancestors of the Cross River population diverged from the western lowland gorilla lineage ~68 kya. Using a diffusion approximation approach to model the genome-wide site frequency spectrum, we infer a history of western lowland gorillas that includes an ancestral population expansion of ~1.4-fold around ~970 kya and a recent ~5.6-fold contraction in population size ~23 kya. The latter may correspond to a major reduction in African equatorial forests around the Last Glacial Maximum. We also analyze patterns of variation among western lowland gorillas to identify several genomic regions with strong signatures of recent selective sweeps. We find that processes related to taste, pancreatic and saliva secretion, sodium ion transmembrane transport, and cardiac muscle function are overrepresented in genomic regions predicted to have experienced recent positive selection. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
    Molecular Biology and Evolution 12/2014; 32(3). DOI:10.1093/molbev/msu394 · 9.11 Impact Factor
    • "There are also anecdotal reports of cross-species (zoonotic) infections of humans with simian or baboon CMVs (Huang et al., 1978; Martin et al., 1994; Michaels et al., 2001), but in two of the three cases the source of infection remained enigmatic. Moreover, phylogenetic analyses suggested interspecies transfer of CMVs between chimpanzees and gorillas (Leendertz et al., 2009; see also Chapter II.22). There is also a report of an experimental infection of laboratory mice (Mus musculus) with a field mouse (Apodemus sylvaticus) isolate (Raynaud and Barreau, 1965). "
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    ABSTRACT: Cytomegaloviruses (CMVs) are highly species specific as they replicate almost exclusively in cells of their natural host species. However, the molecular basis of species specificity remains poorly understood. In cells of a foreign host a post-penetration block to viral gene expression and genome replication appears to restrict viral replication and spread. In some cases, infected cells of a foreign host undergo programmed cell death, indicating that apoptosis acts as a cellular antiviral defence mechanism to prevent viral replication. A few recent studies suggested that mediator and effector molecules of the interferon system and antiviral defences operating at PML nuclear bodies (PML-NBs) might also be involved in restricting the host range of CMVs. Moreover, a recently isolated spontaneous mutant of murine CMV, which is capable of replicating to high titres in human cells, provided a new opportunity to study the mechanisms of CMV host species specificity. In this spontaneously adapted virus, mutations in the region encoding the viral Early1 (E1) proteins were found to be responsible for the extended host range phenotype. Further investigations of the CMV host species specificity should lead to a better understanding of the viral replication machinery, interfering host cell factors, and viral countermeasures.
    Cytomegaloviruses: From Molecular Pathogenesis to Intervention, 2nd edited by Matthias J. Reddehase, 04/2013: chapter I.18: pages 322-329; Caister Academic Press., ISBN: 978-1-908230-18-8
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    • "However, sequences of unknown HCMV variants would remain undetected. This is a serious drawback, in particular because recent discoveries of non-human CMV in both chimpanzees and gorillas revealed a considerably higher diversity than in humans [18]. "
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    ABSTRACT: The known strains of human cytomegalovirus (HCMV) represent genotypic variants of a single species, and HCMV genotypic variability has been studied in order to reveal correlations between different disease patterns and the presence of certain HCMV genotypes, either as single or as multiple infections. The methods used for the detection of HCMV genotypes have not always been sophisticated enough to achieve complete comprehensiveness, mainly because only one genotype is usually detected in a certain specimen, due to primer specificity and genome copy number. To improve detection of variant HCMV genotypes in mixed infections, we developed PCR assays with degenerate primers targeting two variable HCMV genes, glycoprotein B (gB, UL55) and the G-protein-coupled receptor gene UL33. Primers were designed to bind conserved sites in the genomes of HCMV variants and great ape CMVs. To analyse if samples contained one or more HCMV genotypic variants, PCR assays were supplemented with oligonucleotides containing locked nucleic acids. This broad-range PCR methodology and subsequent sequence analysis detected all gB/UL55 and UL33 genotypic variants known to date in primary clinical specimens, but also revealed that many samples contained genotype mixtures. Importantly, a novel UL33 genotypic variant could be discovered in several specimens, and one HCMV isolate was plaque-purified containing the novel UL33 genotype and a so far undescribed variant of gB.
    Virology Journal 11/2009; 6(1):210. DOI:10.1186/1743-422X-6-210 · 2.18 Impact Factor
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