Surveillance of Bat Coronaviruses in Kenya Identifies Relatives of Human Coronaviruses NL63 and 229E and Their Recombination History.

Ying Tao1 Mang Shi2 Christina Chommanard1 Krista Queen1 Jing Zhang1 Wanda Markotter3 Ivan V Kuzmin4 Edward C Holmes2 Suxiang Tong5
Affiliations 5 institutions
  1. Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
  2. Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Life and Environmental Sciences and Sydney Medical School, The University of Sydney, Sydney, Australia.
  3. Centre for Viral Zoonoses, Department of Medical Virology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
  4. Division of High Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
  5. Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA [email protected].

Abstract

Bats harbor a large diversity of coronaviruses (CoVs), several of which are related to zoonotic pathogens that cause severe disease in humans. Our screening of bat samples collected in Kenya from 2007 to 2010 not only detected RNA from several novel CoVs but, more significantly, identified sequences that were closely related to human CoVs NL63 and 229E, suggesting that these two human viruses originate from bats. We also demonstrated that human CoV NL63 is a recombinant between NL63-like viruses circulating in Triaenops bats and 229E-like viruses circulating in Hipposideros bats, with the breakpoint located near 5' and 3' ends of the spike (S) protein gene. In addition, two further interspecies recombination events involving the S gene were identified, suggesting that this region may represent a recombination "hot spot" in CoV genomes. Finally, using a combination of phylogenetic and distance-based approaches, we showed that the genetic diversity of bat CoVs is primarily structured by host species and subsequently by geographic distances.IMPORTANCE Understanding the driving forces of cross-species virus transmission is central to understanding the nature of disease emergence. Previous studies have demonstrated that bats are the ultimate reservoir hosts for a number of coronaviruses (CoVs), including ancestors of severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and human CoV 229E (HCoV-229E). However, the evolutionary pathways of bat CoVs remain elusive. We provide evidence for natural recombination between distantly related African bat coronaviruses associated with Triaenops afer and Hipposideros sp. bats that resulted in a NL63-like virus, an ancestor of the human pathogen HCoV-NL63. These results suggest that interspecies recombination may play an important role in CoV evolution and the emergence of novel CoVs with zoonotic potential.

Supporting text Virus Host Location
Africa 25 bats 46 coronavirus 195 HCoV-229E 4 HCoV-NL63 2 recombination 40 zoonoses 477 Amino Acid Sequence 128 Animals 1949 Chiroptera 372 Conserved Sequence 7 Coronavirus Infections 171 Coronavirus NL63, Human 3 Epidemiological Monitoring 27 Evolution, Molecular 176 Genetic Variation 127 Genome, Viral 317 Kenya 14 Phylogeny 805 Phylogeography 30 Prevalence 62 Recombination, Genetic 59 Respiratory Tract Infections 13 Sequence Analysis, DNA 113

Evidence records

5 total
Zoonotic Surveillance
1 records · 1 evidence types
Evidence type
1 records
OVE2495
Key finding

RNA from several novel coronaviruses, including sequences closely related to human CoVs NL63 and 229E, was detected in bat samples from Kenya.

Virus
Host
Location
Supporting text

Our screening of bat samples collected in Kenya from 2007 to 2010 not only detected RNA from several novel CoVs but, more significantly, identified sequences that were closely related to human CoVs NL63 and 229E.

Method
RNA detection | sequencing
Sample type
bat samples
Geographic raw
Kenya
Country inferred
KEN
Genomic Evolution
4 records · 2 evidence types
Evidence type
3 records
OVE2496
Key finding

Human CoV NL63 was shown to be a recombinant between NL63-like viruses from Triaenops bats and 229E-like viruses from Hipposideros bats, with breakpoints near both ends of the spike gene.

Virus
Host
Not specified
Location
Not specified
Supporting text

We also demonstrated that human CoV NL63 is a recombinant between NL63-like viruses circulating in Triaenops bats and 229E-like viruses circulating in Hipposideros bats, with the breakpoint located near 5' and 3' ends of the spike (S) protein gene.

Event type
recombination
Genes or segments
spike (S) protein gene
OVE2498
Key finding

Natural recombination between African bat coronaviruses associated with Triaenops afer and Hipposideros species resulted in an NL63-like virus ancestral to HCoV-NL63.

Virus
Host
Not specified
Location
Not specified
Supporting text

We provide evidence for natural recombination between distantly related African bat coronaviruses associated with Triaenops afer and Hipposideros sp. bats that resulted in a NL63-like virus, an ancestor of the human pathogen HCoV-NL63.

Event type
recombination
OVE2497
Key finding

Two additional interspecies recombination events involving the spike gene of bat coronaviruses were identified, indicating a recombination hotspot region in CoV genomes.

Virus
Host
Not specified
Location
Not specified
Supporting text

In addition, two further interspecies recombination events involving the S gene were identified, suggesting that this region may represent a recombination 'hot spot' in CoV genomes.

Event type
recombination
Genes or segments
spike (S) gene
Evidence type
1 records
OVE2499
Key finding

Phylogenetic and distance-based analyses indicated that bat coronavirus genetic diversity is structured primarily by host species and secondarily by geographic distance.

Virus
Host
Location
Not specified
Supporting text

Using a combination of phylogenetic and distance-based approaches, we showed that the genetic diversity of bat CoVs is primarily structured by host species and subsequently by geographic distances.

Analysis methods
phylogenetic analysis | distance-based analysis