Temporal and coevolutionary analyses reveal the events driving the emergence and circulation of human mamastroviruses

ABSTRACT

Characterized by high genetic diversity, broad host range, and resistance to adverse conditions, coupled with recent reports of neurotropic astroviruses circulating in humans, mamastroviruses pose a threat to public health. The current astrovirus classification system based on host source prevents determining whether strains with distinct tropism or virulence are emerging. By using integrated phylogeny, we propose a standardized demarcation of species and genotypes, with reproducible cut-off values that reconcile the pairwise sequence distribution, genetic distances between lineages, and the topological reconstruction of the Mamastrovirus genus. We further define the various links established by co-evolution and resolve the dynamics of transmission chains to identify host-jump events and the sources from which different mamastrovirus species circulating in humans have emerged. We observed that recombination is relatively infrequent and restricted to within genotypes. The well-known “human” astrovirus, defined here as mamastrovirus species 7, has co-speciated with humans, while there have been two additional host-jumps into humans from distinct hosts. Newly defined species 6 genotype 2, linked to severe gastroenteritis in children, resulted from a marmot to human jump taking place ∼200 years ago while species 6 genotype 7 (MastV-Sp6Gt7), linked to neurological disease in immunocompromised patients, jumped from bovines only ∼50 years ago. Through demographic reconstruction, we determined that the latter reached coalescent viral population growth only 20 years ago and is evolving at a much higher evolutionary rate than other genotypes infecting humans. This study constitutes mounting evidence of MastV-Sp6Gt7 active circulation and highlights the need for diagnostics capable of detecting it.

KEYWORDS:

• Mamastrovirus
• Bayesian inference of phylogeny
• host-jump event
• pairwise sequence comparison
• cospeciation
• zoonotic emergence

Acknowledgments

We thank Dr. Gregory S. Orf for assistance with a parsing script in R. Author Contributions: Conceptualization, LJP and MGB; methodology, LJP and MGB; software, LJP; validation, KF, LJP; formal analysis, KF, LJP and MGB; investigation, KF, LJP and MGB; data curation, KF LJP and MGB; writing original draft preparation, LJP and MGB; writing – review and editing, LJP, MGB and GAC; visualization, LJP and MGB; supervision, GAC; project administration, MGB and GAC; funding acquisition GAC. All authors have read and agreed to the published version of the manuscript.

Disclosure statement

LJP, KF, MGB, and GAC are all employees and Abbott shareholders.

Data availability

Accessions with relevant metadata are contained in Supplemental Tables S1 and S2. Scripts for generating figures are available upon request. Raw data files for the analysis of coevolutionary analysis using PACo, JANE and the temporal analysis using BEAST are available on Github at https://github.com/LesterJP/Temporal-and-coevolutionary-analyses-reveal-the-events-driving-the-emergence-and-circulation-of-huma.