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A Novel Subtype of Bovine Hepacivirus Identified in Ticks Reveals the Genetic Diversity and Evolution of Bovine Hepacivirus.

ABSTRACT: Hepaciviruses represent a group of viruses that pose a significant threat to the health of humans and animals. New members of the genus Hepacivirus in the family Flaviviridae have recently been identified in a wide variety of host species worldwide. Similar to the Hepatitis C virus (HCV), bovine hepacivirus (BovHepV) is hepatotropic and causes acute or persistent infections in cattle. BovHepVs are distributed worldwide and classified into two genotypes with seven subtypes in genotype 1. In this study, three BovHepV strains were identified in the samples of ticks sucking blood on cattle in the Guangdong province of China, through unbiased high-throughput sequencing. Genetic analysis revealed the polyprotein-coding gene of these viral sequences herein shared 67.7-84.8% nt identity and 76.1-95.6% aa identity with other BovHepVs identified worldwide. As per the demarcation criteria adopted for the genotyping and subtyping of HCV, these three BovHepV strains belonged to a novel subtype within the genotype 1. Additionally, purifying selection was the dominant evolutionary pressure acting on the genomes of BovHepV, and genetic recombination was not common among BovHepVs. These results expand the knowledge about the genetic diversity and evolution of BovHepV distributed globally, and also indicate genetically divergent BovHepV strains were co-circulating in cattle populations in China.

SUBMITTER: Shao JW

PROVIDER: S-EPMC8623979 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundMembers of the order Chlamydiales are known for their potential as human and veterinary bacterial pathogens. Despite this recognition, epidemiological factors such as routes of transmission are yet to be fully defined. Ticks are well known vectors for many other infections with several reports recently describing the presence of bacteria in the order Chlamydiales in these arthropods. Australian wildlife are hosts to an extensive range of tick species. Evidence is also growing that the marsupial hosts these ticks parasitise can also be infected by a number of bacteria in the order Chlamydiales, with at least one species, Chlamydia pecorum, posing a significant conservation threat. In the current study, we investigated the presence and identity of Chlamydiales in 438 ixodid ticks parasitizing wildlife in Australia by screening with a pan-Chlamydiales specific targeting the 16S rRNA gene.ResultsPan-Chlamydiales specific PCR assays confirmed the common presence of Chlamydiales in Australian ticks parasitising a range of native wildlife. Interestingly, we did not detect any Chlamydiaceae, including C. pecorum, the ubiquitous pathogen of the koala. Instead, the Chlamydiales diversity that could be resolved indicated that Australian ticks carry at least six novel Chlamydiales genotypes. Phylogenetic analysis of the 16S rRNA sequences (663 bp) of these novel Chlamydiales suggests that three of these genotypes are associated with the Simkaniaceae and putatively belong to three distinct novel strains of Fritschea spp. and three genotypes are related to the "Ca. Rhabdochlamydiaceae" and putatively belong to a novel genus, Rhabdochlamydia species and strain, respectively.ConclusionsSequence results suggest Australian wildlife ticks harbour a range of unique Chlamydiales bacteria that belong to families previously identified in a range of arthropod species. The results of this work also suggest that it is unlikely that arthropods act as vectors of pathogenic members of the family Chlamydiaceae, including C. pecorum, in Australian wildlife. The biology of novel Chlamydiales identified in arthropods remain unknown. The pathogenic role of the novel Chlamydiales identified in this study and the role that ticks may play in their transmission needs to be explored further.

Project description:In recent years, hepatitis C virus (HCV)-related viruses were identified in several species, including dogs, horses, bats, and rodents. In addition, a novel virus of the genus Hepacivirus has been discovered in bovine samples and was termed bovine hepacivirus (BovHepV). Prediction of the BovHepV internal ribosome entry site (IRES) structure revealed strong similarities to the HCV IRES structure comprising domains II, IIIabcde, pseudoknot IIIf, and IV with the initiation codon AUG. Unlike HCV, only one microRNA-122 (miR-122) binding site could be identified in the BovHepV 5' nontranslated region. In this study, we analyzed the necessity of BovHepV IRES domains to initiate translation and investigated possible interactions between the IRES and core coding sequences by using a dual luciferase reporter assay. Our results suggest that such long-range interactions within the viral genome can affect IRES-driven translation. Moreover, the significance of a possible miR-122 binding to the BovHepV IRES was investigated. When analyzing translation in human Huh-7 cells with large amounts of endogenous miR-122, introduction of point mutations to the miR-122 binding site resulted in reduced translation efficiency. Similar results were observed in HeLa cells after substitution of miR-122. Nevertheless, the absence of pronounced effects in a bovine hepatocyte cell line expressing hardly any miR-122 as well suggests additional functions of this host factor in virus replication.IMPORTANCE Several members of the family Flaviviridae, including HCV, have adapted cap-independent translation strategies to overcome canonical eukaryotic translation pathways and use cis-acting RNA-elements, designated viral internal ribosome entry sites (IRES), to initiate translation. Although novel hepaciviruses have been identified in different animal species, only limited information is available on their biology on molecular level. Therefore, our aim was a fundamental analysis of BovHepV IRES functions. The findings which show that functional IRES elements are also crucial for BovHepV translation expand our knowledge on molecular mechanism of hepacivirus propagation. We also studied the possible effects of one major host factor implicated in HCV pathogenesis, miR-122. The results of mutational analyses suggested that miR-122 enhances virus translation mediated by BovHepV IRES.

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A Novel Subtype of Bovine Hepacivirus Identified in Ticks Reveals the Genetic Diversity and Evolution of Bovine Hepacivirus.

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