Characterization of a novel betacoronavirus related to middle East respiratory syndrome coronavirus in European hedgehogs - PubMed (original) (raw)

Victor Max Corman et al. J Virol. 2014 Jan.

Abstract

Bats are known to host viruses closely related to important human coronaviruses (HCoVs), such as HCoV-229E, severe-acute respiratory syndrome coronavirus (SARS-CoV), and Middle East respiratory syndrome CoV (MERS-CoV). As RNA viruses may coevolve with their hosts, we sought to investigate the closest sister taxon to bats, the Eulipotyphla, and screened European hedgehogs (Erinaceus europaeus) from Germany for CoV by nested reverse transcriptase PCR. A novel betacoronavirus species in a phylogenetic sister relationship to MERS-CoV and clade c bat CoVs was detected and characterized on the whole-genome level. A total of 58.9% of hedgehog fecal specimens were positive for the novel CoV (EriCoV) at 7.9 log10 mean RNA copies per ml. EriCoV RNA concentrations were higher in the intestine than in other solid organs, blood, or urine. Detailed analyses of the full hedgehog intestine showed the highest EriCoV concentrations in lower gastrointestinal tract specimens, compatible with viral replication in the lower intestine and fecal-oral transmission. Thirteen of 27 (48.2%) hedgehog sera contained non-neutralizing antibodies against MERS-CoV. The animal origins of this betacoronavirus clade that includes MERS-CoV may thus include both bat and nonbat hosts.

PubMed Disclaimer

Figures

FIG 1

FIG 1

Betacoronavirus phylogeny, including the novel viruses from European hedgehogs. Bayesian phylogeny of an 816-nucleotide RdRp gene sequence fragment corresponding to positions 14822 to 15637 in MERS-CoV strain EMC/2012 (GenBank accession no. JX869059). The novel Erinaceus viruses are shown in red, and MERS-CoVs in blue.

FIG 2

FIG 2

Erinaceus CoV RNA concentrations in solid organs, urine, and blood, and virus distribution within the intestine. (A) Virus concentrations in solid organs, urine, and blood of 12 EriCoV-positive animals are given in log10 RNA copies per milliliter or gram of tissue. Horizontal bars represent mean virus concentrations per organ category. Missing bars represent negative test results. For all organs, specimens from 12 individual animals were available, except urine, where no specimen was available from animal 12. Colors represent individual animals as identified in the key. (B) Ranges of EriCoV concentrations in 10 different intestinal sections of five RNA-positive individuals are given in log10 RNA copies per gram of tissue. Black horizontal bars represent mean virus concentrations; ***, P < 0.005 according to Mann-Whitney U test.

FIG 3

FIG 3

Serologic testing of hedgehog blood. (Top) Reaction patterns of a reactive (23) and a nonreactive (22) hedgehog serum with MERS-CoV-infected Vero cells at 1:10 screening dilution. (Bottom) Endpoint dilution of serum sample 23. Scale bar, 20 μm.

FIG 4

FIG 4

Genome organization of EriCoV and other clade c betacoronaviruses. Genomes are represented by black lines, and ORFs are indicated by gray arrows. The ribosomal frameshift site (RFS) at nucleotide positions 13578 to 13584 (EriCoV/2012-174) and 13605 to 13611 (EriCoV/2012-216) is marked with a black arrow. The locations of transcription regulatory core sequences (TRS) are marked by labeled dots.

FIG 5

FIG 5

Genomic sequence identity between EriCoVs and other clade c betacoronaviruses. Similarity plots were generated using SSE version 1.0 (38) using a sliding window of 400 and a step size of 40 nucleotides.

FIG 6

FIG 6

Phylogenies of all ORFs, including the novel hedgehog betacoronaviruses. Statistical support of grouping from Bayesian posterior probabilities is shown at deep nodes. For graphical reasons, only values above 0.7 are shown. Scale bar represents genetic distance. The novel Erinaceus viruses are shown in red, and MERS-CoVs in blue.

References

    1. Adams MJ, Carstens EB. 2012. Ratification vote on taxonomic proposals to the International Committee on Taxonomy of Viruses (2012). Arch. Virol. 157:1411–1422. 10.1007/s00705-012-1299-6 - DOI - PMC - PubMed
    1. Perlman S, Netland J. 2009. Coronaviruses post-SARS: update on replication and pathogenesis. Nat. Rev. Microbiol. 7:439–450. 10.1038/nrmicro2147 - DOI - PMC - PubMed
    1. Hamre D, Procknow JJ. 1966. A new virus isolated from the human respiratory tract. Proc. Soc. Exp. Biol. Med. 121:190–193. 10.3181/00379727-121-30734 - DOI - PubMed
    1. van der Hoek L, Pyrc K, Jebbink MF, Vermeulen-Oost W, Berkhout RJ, Wolthers KC, Wertheim-van Dillen PM, Kaandorp J, Spaargaren J, Berkhout B. 2004. Identification of a new human coronavirus. Nat. Med. 10:368–373. 10.1038/nm1024 - DOI - PMC - PubMed
    1. Drosten C, Gunther S, Preiser W, van der Werf S, Brodt HR, Becker S, Rabenau H, Panning M, Kolesnikova L, Fouchier RA, Berger A, Burguiere AM, Cinatl J, Eickmann M, Escriou N, Grywna K, Kramme S, Manuguerra JC, Muller S, Rickerts V, Sturmer M, Vieth S, Klenk HD, Osterhaus AD, Schmitz H, Doerr HW. 2003. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N. Engl. J. Med. 348:1967–1976. 10.1056/NEJMoa030747 - DOI - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources