Discovery of two highly divergent negative-sense RNA viruses associated with the parasitic nematode, Capillaria hepatica, in wild Mus musculus from New York City

Abstract

Recent advances in high-throughput sequencing technology have led to a rapid expansion in the number of viral sequences associated with samples from vertebrates, invertebrates and environmental samples. Accurate host identification can be difficult in assays of complex samples that contain more than one potential host. Using unbiased metagenomic sequencing, we investigated wild house mice (Mus musculus) and brown rats (Rattus norvegicus) from New York City to determine the aetiology of liver disease. Light microscopy was used to characterize liver disease, and fluorescent microscopy with in situ hybridization was employed to identify viral cell tropism. Sequences representing two novel negative-sense RNA viruses were identified in homogenates of wild house mouse liver tissue: Amsterdam virus and Fulton virus. In situ hybridization localized viral RNA to Capillaria hepatica, a parasitic nematode that had infected the mouse liver. RNA from either virus was found within nematode adults and unembryonated eggs. Expanded PCR screening identified brown rats as a second rodent host for C. hepatica as well as both nematode-associated viruses. Our findings indicate that the current diversity of nematode-associated viruses may be underappreciated and that anatomical imaging offers an alternative to computational host assignment approaches.

Embracing the heterogeneity of natural viruses in mouse studies

“…One difficulty in studying wild mice is controlling for timing and source of pathogen exposure. Wild mice captured in California, Virginia and New York City led to the identification of many novel viruses including murine astrovirus and Kobuvirus [2,10,32]. Evaluation of wild mice has also revealed complex trans-kingdom interactions.…”

DsRNA Sequencing for RNA Virus Surveillance Using Human Clinical Samples

“…The Fulton virus consists of three segments (L, M, S) and is a negative-sense RNA virus. This virus was recently reported to have been detected in wild rodents in New York City [ 28 ]. It was reported that the Fulton virus was related to Bunyavirales families and was associated with liver disease in wild rodents.…”

In action—an early warning system for the detection of unexpected or novel pathogens

“…In this analysis, representatives of the four established genera in the family Peribunyaviridae were considered, namely Orthobunyavirus, Herbevirus, Pacuvirus, and Shangavirus ( Hughes et al., 2020 ). In addition, other related unclassified members of the family Peribunyaviridae that are listed by the International Committee on Taxonomy of Viruses ( Hughes et al., 2020 ), encompassing Akhtuba virus ( Quan et al., 2013a ), Fulton virus ( Williams et al., 2019 ), Khurdun virus ( Al’kovskhovsk et al., 2013 ), Lakamha virus ( Kopp et al., 2019 ), and largemouth bass bunyavirus ( Waltzek et al., 2019 ) were included (Supplementary Table S6; results of pairwise sequence comparisons of representative viruses see Supplementary Table S7). Some of these viruses were assigned to the recently proposed new genera Lakivirus, Lambavirus , and Khurdivirus ( Fig.…”