Dataset Information

Roles of host small RNAs in the evolution and host tropism of coronaviruses.

ABSTRACT: Human coronaviruses (CoVs) can cause respiratory infection epidemics that sometimes expand into globally relevant pandemics. All human CoVs have sister strains isolated from animal hosts and seem to have an animal origin, yet the process of host jumping is largely unknown. RNA interference (RNAi) is an ancient mechanism in many eukaryotes to defend against viral infections through the hybridization of host endogenous small RNAs (miRNAs) with target sites in invading RNAs. Here, we developed a method to identify potential RNAi-sensitive sites in the viral genome and discovered that human-adapted coronavirus strains had deleted some of their sites targeted by miRNAs in human lungs when compared to their close zoonic relatives. We further confirmed using a phylogenetic analysis that the loss of RNAi-sensitive target sites could be a major driver of the host-jumping process, and adaptive mutations that lead to the loss-of-target might be as simple as point mutation. Up-to-date genomic data of severe acute respiratory syndrome coronavirus 2 and Middle-East respiratory syndromes-CoV strains demonstrate that the stress from host miRNA milieus sustained even after their epidemics in humans. Thus, this study illustrates a new mechanism about coronavirus to explain its host-jumping process and provides a novel avenue for pathogenesis research, epidemiological modeling, and development of drugs and vaccines against coronavirus, taking into consideration these findings.

SUBMITTER: Meng Q

PROVIDER: S-EPMC7929378 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Roles of host small RNAs in the evolution and host tropism of coronaviruses.

Meng Qingren Q Chu Yanan Y Shao Changjun C Chen Jing J Wang Jian J Gao Zhancheng Z Yu Jun J Kang Yu Y

Briefings in bioinformatics 20210301 2

Human coronaviruses (CoVs) can cause respiratory infection epidemics that sometimes expand into globally relevant pandemics. All human CoVs have sister strains isolated from animal hosts and seem to have an animal origin, yet the process of host jumping is largely unknown. RNA interference (RNAi) is an ancient mechanism in many eukaryotes to defend against viral infections through the hybridization of host endogenous small RNAs (miRNAs) with target sites in invading RNAs. Here, we developed a me ...[more]

PMID: 33587745

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Project description:Controlling many infectious diseases, including SARS-Coronavirus-2 (SARS-CoV-2), requires surveillance followed by isolation, contact-tracing and quarantining. These interventions often begin by identifying symptomatic individuals. However, actively removing pathogen strains causing symptomatic infections may inadvertently select for strains less likely to cause symptomatic infections. Moreover, a pathogen's fitness landscape is structured around a heterogeneous host pool; uneven surveillance efforts and distinct transmission risks across host classes can meaningfully alter selection pressures. Here, we explore this interplay between evolution caused by disease control efforts and the evolutionary consequences of host heterogeneity. Using an evolutionary epidemiology model parameterized for coronaviruses, we show that intense symptoms-driven disease control selects for asymptomatic strains, particularly when these efforts are applied unevenly across host groups. Under these conditions, increasing quarantine efforts have diverging effects. If isolation alone cannot eradicate, intensive quarantine efforts combined with uneven detections of asymptomatic infections (e.g., via neglect of some host classes) can favor the evolution of asymptomatic strains. We further show how, when intervention intensity depends on the prevalence of symptomatic infections, higher removal efforts (and isolating symptomatic cases in particular) more readily select for asymptomatic strains than when these efforts do not depend on prevalence. The selection pressures on pathogens caused by isolation and quarantining likely lie between the extremes of no intervention and thoroughly successful eradication. Thus, analyzing how different public health responses can select for asymptomatic pathogen strains is critical for identifying disease suppression efforts that can effectively manage emerging infectious diseases.Supplementary informationThe online version contains supplementary material available at 10.1007/s11071-022-07548-7.

Project description:microRNAs (miRNAs), a class of short, non-coding RNA can be found in a highly stable, cell-free form in mammalian body fluids. Specific miRNAs are secreted by parasitic nematodes in exosomes and have been detected in the serum of murine and dog hosts infected with the filarial nematodes Litomosoides sigmodontis and Dirofilaria immitis, respectively. Here we identify extracellular, parasite-derived small RNAs associated with Onchocerca species infecting cattle and humans.Small RNA libraries were prepared from total RNA extracted from the nodule fluid of cattle infected with Onchocerca ochengi as well as serum and plasma from humans infected with Onchocerca volvulus in Cameroon and Ghana. Parasite-derived miRNAs were identified based on the criteria that sequences unambiguously map to hairpin structures in Onchocerca genomes, do not align to the human genome and are not present in European control serum.A total of 62 mature miRNAs from 52 distinct pre-miRNA candidates were identified in nodule fluid from cattle infected with O. ochengi of which 59 are identical in the genome of the human parasite O. volvulus. Six of the extracellular miRNAs were also identified in sequencing analyses of serum and plasma from humans infected with O. volvulus. Based on sequencing analysis the abundance levels of the parasite miRNAs in serum or plasma range from 5 to 127 reads/per million total host miRNA reads identified, comparable to our previous analyses of Schistosoma mansoni and L. sigmodontis miRNAs in serum. All six of the O. volvulus miRNAs identified have orthologs in other filarial nematodes and four were identified in the serum of mice infected with L. sigmodontis.We have identified parasite-derived miRNAs associated with onchocerciasis in cattle and humans. Our results confirm the conserved nature of RNA secretion by diverse nematodes. Additional species-specific small RNAs from O. volvulus may be present in serum based on the novel miRNA sequences identified in the nodule fluid. In our analyses comparison to European control serum illuminates the scope for false-positives, warranting caution in criteria that should be applied to identification of biomarkers of infection.

Dataset Information

Roles of host small RNAs in the evolution and host tropism of coronaviruses.

Publications

Roles of host small RNAs in the evolution and host tropism of coronaviruses.

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