Full Genome Nobecovirus Sequences From Malagasy Fruit Bats Define a Unique Evolutionary History for This Coronavirus Clade.

Gwenddolen Kettenburg,Ny Anjara Fifi Ravelomanantsoa,Angelo Andrianiaina,Philippe Dussart,Santino Andry,Cara E Brook,Joseph L Derisi,Vida Ahyong,Vololoniaina Raharinosy,Anecia Gentles,Cristina M Tato,Hafaliana Christian Ranaivoson,Amy Kistler,Tsiry Hasina Randriambolamanantsoa,Jean-Michel Heraud

doi:10.3389/fpubh.2022.786060

Abstract

Bats are natural reservoirs for both Alpha- and Betacoronaviruses and the hypothesized original hosts of five of seven known zoonotic coronaviruses. To date, the vast majority of bat coronavirus research has been concentrated in Asia, though coronaviruses are globally distributed; indeed, SARS-CoV and SARS-CoV-2-related Betacoronaviruses in the subgenus Sarbecovirus have been identified circulating in Rhinolophid bats in both Africa and Europe, despite the relative dearth of surveillance in these regions. As part of a long-term study examining the dynamics of potentially zoonotic viruses in three species of endemic Madagascar fruit bat (Pteropus rufus, Eidolon dupreanum, Rousettus madagascariensis), we carried out metagenomic Next Generation Sequencing (mNGS) on urine, throat, and fecal samples obtained from wild-caught individuals. We report detection of RNA derived from Betacoronavirus subgenus Nobecovirus in fecal samples from all three species and describe full genome sequences of novel Nobecoviruses in P. rufus and R. madagascariensis. Phylogenetic analysis indicates the existence of five distinct Nobecovirus clades, one of which is defined by the highly divergent ancestral sequence reported here from P. rufus bats. Madagascar Nobecoviruses derived from P. rufus and R. madagascariensis demonstrate, respectively, Asian and African phylogeographic origins, mirroring those of their fruit bat hosts. Bootscan recombination analysis indicates significant selection has taken place in the spike, nucleocapsid, and NS7 accessory protein regions of the genome for viruses derived from both bat hosts. Madagascar offers a unique phylogeographic nexus of bats and viruses with both Asian and African phylogeographic origins, providing opportunities for unprecedented mixing of viral groups and, potentially, recombination. As fruit bats are handled and consumed widely across Madagascar for subsistence, understanding the landscape of potentially zoonotic coronavirus circulation is essential for mitigation of future zoonotic threats.

Highlights

In the past 20 years, bat-derived coronaviruses SARS-CoV, MERS-CoV, and SARS-CoV-2 have been responsible for two deadly epidemics and the ongoing COVID-19 pandemic [1–4]
The R. madagascariensis Nobecoviruses, by contrast, showed >90% amino acid and nucleotide similarity to the E. helvum African lineage throughout Orf1ab, but both P. rufus and R. madagascariensis sequences diverged from all other reference genomes in the first half of the spike protein, which corresponds to the S1 subunit and includes the receptor binding domain that mediates viral entry into host cells [95]
We contribute three full-length genome sequences and four RNAdependent RNA polymerase (RdRp) fragments to public NCBI repositories; these sequences correspond to at least two novel Nobecoviruses derived from wild Malagasy fruit bats, Pteropus rufus and Rousettus madagascariensis, with evidence of additional genetic variants circulating in Eidolon dupreanum, as well

Summary

Introduction

In the past 20 years, bat-derived coronaviruses SARS-CoV, MERS-CoV, and SARS-CoV-2 have been responsible for two deadly epidemics and the ongoing COVID-19 pandemic [1–4]. These coronaviruses (CoVs) are members of the Betacoronavirus genus, which, along with genus Alphacoronavirus, are primarily associated with bat hosts [1–4]; the remaining CoV genera, Gammacoronavirus and Deltacoronavirus, are typically hosted by birds [5]. Since the emergence of SARS-CoV in 2002, there has been increasing interest in surveying potential hosts of coronaviruses and contributing new virus sequences to public databases, with most effort focused on sampling bats from Asia [19–28], the continent of origin for both the SARSCoV epidemic and the SARS-CoV-2 pandemic. More concerted efforts have arisen to survey the landscape of bat-borne coronaviruses in other regions of the world, including Africa and Europe [11, 12, 29–33]

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