@article{23a7c03463c94b46997a9ab35140d2f8,
title = "Evolution of anelloviruses from a circovirus-like ancestor through gradual augmentation of the jelly-roll capsid protein",
abstract = "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 {\textquoteleft}healthy virome{\textquoteright}. 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 Anelloviridae to a new phylum, {\textquoteleft}Commensaviricota{\textquoteright}, and including it into the kingdom Shotokuvirae (realm Monodnaviria), alongside Cressdnaviricota and Cossaviricota.",
keywords = "Anellovirus, Commensaviricota, capsid proteins, jelly-roll fold, structural modelling, taxonomy and classification, virus evolution",
author = "Anamarija Butkovic and Simona Kraberger and Zoe Smeele and Martin, {Darren P.} and Kara Schmidlin and Fontenele, {Rafaela S.} and Shero, {Michelle R.} and Beltran, {Roxanne S.} and Kirkham, {Amy L.} and Maketalena Aleamotu'a and Burns, {Jennifer M.} and Koonin, {Eugene V.} and Arvind Varsani and Mart Krupovic",
note = "Funding Information: A.B. was supported by a post-doctoral fellowship from Foundation pour la Recherche M{\`e}dicale (grant number SPF202110014092). M.K. was supported by a grant from the l{\textquoteright}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). Funding Information: 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{\textquoteright}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. Funding Information: A.B. was supported by a post-doctoral fellowship from Foundation pour la Recherche M{\`e}dicale (grant number SPF202110014092). M.K. was supported by a grant from the l{\textquoteright}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{\textquoteright}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. The content is solely the responsibility of the authors and does not necessarily reflect the official views of the NIH. J.M.B. contributed to this work while serving at the National Science Foundation. Any opinion, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation. The findings and conclusions in this article are those of the authors and do not necessarily represent the views of the US Fish and Wildlife Service. Collection of grizzly bear fecal samples was undertaken by Daniel Thompson and Kent Schmidlin at the Wyoming Game and Fish Department (Lander, Wyoming, USA) and the team at Trophy Game (USA). Funding Information: 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. Publisher Copyright: {\textcopyright} The Author(s) 2023. Published by Oxford University Press.",
year = "2023",
doi = "10.1093/ve/vead035",
language = "English (US)",
volume = "9",
journal = "Virus Evolution",
issn = "2057-1577",
publisher = "Oxford University Press",
number = "1",
}