Evolution of anelloviruses from a circovirus-like ancestor through gradual augmentation of the jelly-roll capsid protein

• Published in: Virus Evolution
• Main Authors: Butkovic, Anamarija, Kraberger, Simona, Smeele, Zoe, Martin, Darren, Schmidlin, Kara, Fontenele, Rafaela, Shero, Michelle, Beltran, Roxanne, Kirkham, Amy, Aleamotu’a, Maketalena, Burns, Jennifer, Koonin, Eugene, Varsani, Arvind, Krupovic, Mart
• Other Authors: Virologie des archées - Archaeal Virology, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur Paris (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur Paris (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Arizona State University Tempe (ASU), University of Cape Town, Woods Hole Oceanographic Institution (WHOI), University of California Santa Cruz (UC Santa Cruz), University of California (UC), US Fish and Wildlife Service, Newcastle University Newcastle, Texas Tech University Lubbock (TTU), National Center for Biotechnology Information (NCBI), National Institutes of Health Bethesda (NIH), A.B. was supported by a post-doctoral fellowship from Foundation pour la Recherche Mèdicale (grant number SPF202110014092). M.K. was supported by a grant from the l’Agence Nationale de la Recherche (ANR-20-CE20-0009-02). A.L.K. and R.S.B. were supported by Institutional Development Awards (IDeA) Networks of Biomedical Research Excellence Assistantships (grant number P20GM103395) from the National Institute of General Medical Sciences of the National Institutes of Health (NIH). E.V.K. was supported by the Intramural Research Program of the NIH (National Library of Medicine).Weddell seal samples were collected under National Marine Fisheries Service Marine Mammal permit #17411, Antarctic Conservation Act permit #2014-003, and the University of Alaska Anchorage and University of Alaska Fairbanks’s Institutional Animal Care and Use Committee approvals #419971 and #854089, with funding from the National Science Foundation grant ANT-1246463 to J.M.B.The molecular work described in this study is supported by the Center of Evolution and Medicine Venture Fund (Center of Evolution and Medicine, Arizona State University, USA) grant awarded to A.V., ANR-20-CE20-0009,VIROMET,Devoiler le virome des archées methanogenes(2020)
• Format: Article in Journal/Newspaper
• Language: English
• Published: HAL CCSD 2023
• Subjects: Anellovirus; structural modelling; capsid proteins; jelly-roll fold; virus evolution; taxonomy and classification; Commensaviricota; [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology; Weddell; Antarc*; Antarctica; Ursus arctos; Weddell Seal
• Online Access: https://pasteur.hal.science/pasteur-04131608; https://pasteur.hal.science/pasteur-04131608/document; https://pasteur.hal.science/pasteur-04131608/file/Butkovic2023VirusEvol.pdf; https://doi.org/10.1093/ve/vead035

International audience Anelloviruses are highly prevalent in diverse mammals, including humans, but so far have not been linked to any disease and are considered to be part of the ‘healthy virome’. These viruses have small circular single-stranded DNA (ssDNA) genomes and encode several proteins with no detectable sequence similarity to proteins of other known viruses. Thus, anelloviruses are the only family of eukaryotic ssDNA viruses currently not included in the realm Monodnaviria. To gain insights into the provenance of these enigmatic viruses, we sequenced more than 250 complete genomes of anelloviruses from nasal and vaginal swab samples of Weddell seal (Leptonychotes weddellii) from Antarctica and a fecal sample of grizzly bear (Ursus arctos horribilis) from the USA and performed a comprehensive family-wide analysis of the signature anellovirus protein ORF1. Using state-of-the-art remote sequence similarity detection approaches and structural modeling with AlphaFold2, we show that ORF1 orthologs from all Anelloviridae genera adopt a jelly-roll fold typical of viral capsid proteins (CPs), establishing an evolutionary link to other eukaryotic ssDNA viruses, specifically, circoviruses. However, unlike CPs of other ssDNA viruses, ORF1 encoded by anelloviruses from different genera display remarkable variation in size, due to insertions into the jelly-roll domain. In particular, the insertion between β-strands H and I forms a projection domain predicted to face away from the capsid surface and function at the interface of virus–host interactions. Consistent with this prediction and supported by recent experimental evidence, the outermost region of the projection domain is a mutational hotspot, where rapid evolution was likely precipitated by the host immune system. Collectively, our findings further expand the known diversity of anelloviruses and explain how anellovirus ORF1 proteins likely diverged from canonical jelly-roll CPs through gradual augmentation of the projection domain. We suggest assigning ...