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.

Leveraging machine learning for taxonomic classification of emerging astroviruses

“…are located in Cloud 1. Moreover, all 13 MAstV-Sp6G2 sequences and all 18 MAstV-Sp6G7 sequences analyzed in Perez et al (2023) are separated from Cloud 1 and located in the main cloud (the sequences located between the two separating planes). This suggests a correspondence between the Cloud 1 sequences and MAstV-Sp7G3 sequences.…”

“…Given the mounting evidence for different serotypes, clades, and genotypes associated with unique cross-species transmissions, different rates of evolution and intraspecific recombination for human astroviruses (HAstV) ( Bosch et al, 2014 ; Donato and Vijaykrishna, 2017 ; Hargest et al, 2021 ; Perez et al, 2023 ) and goose astroviruses (GoAstV) ( Fei et al, 2022 ; Zhu and Sun, 2022 ), we further investigated the sequences belonging to these two subgroups. Figure 4 displays a visualization of the 6-mer counts of the genomes in Dataset 2 ( Mamastrovirus and Avastrovirus genomes with established labels), together with the 191 genomes with genus labels predicted by 3PCM with the use of principal component analysis (PCA).…”

“…This suggests that a HAstV subgenus exists within the genus Mamastrovirus. A comparison between Cloud 1 and the human Mamastroviruses sequences analyzed in Perez et al (2023) reveals that all the 91 MAstV-Sp7G3 human astrovirus sequences included in our analysis (not collected from sewage, not collected from an unknown host, etc.) are located in Cloud 1.…”

Antigenic determinants of HAstV-VA1 neutralization and their relevance in the human immune response

“…Also, a growing number of newly identified neurotropic astroviruses have been identified in cases of nonsuppurative encephalitis and neurological disease in pigs, ruminant species (cattle, sheep), and minks, changing the perception on the role of these viruses in non-enteric diseases (9). Mammalian astroviruses have high genetic diversity, are highly ubiquitous, and have a broad host range (10). Evolutionary analyses suggest sustained and extensive cross-species transmission events have occurred in the past between wild and domestic animal species and humans (10)(11)(12)(13).…”

“…Mammalian astroviruses have high genetic diversity, are highly ubiquitous, and have a broad host range (10). Evolutionary analyses suggest sustained and extensive cross-species transmission events have occurred in the past between wild and domestic animal species and humans (10)(11)(12)(13). In this context, studying human and animal astroviruses is warranted as part of a One Health approach and in preparation for future zoonotic events.…”