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Viruses Apr 2021Oncolytic reovirus preferentially targets and kills cancer cells via the process of oncolysis, and additionally drives clinically favorable antitumor T cell responses... (Review)
Review
Oncolytic reovirus preferentially targets and kills cancer cells via the process of oncolysis, and additionally drives clinically favorable antitumor T cell responses that form protective immunological memory against cancer relapse. This two-prong attack by reovirus on cancers constitutes the foundation of its use as an anticancer oncolytic agent. Unfortunately, the efficacy of these reovirus-driven antitumor effects is influenced by the highly suppressive tumor microenvironment (TME). In particular, the myeloid cell populations (e.g., myeloid-derived suppressive cells and tumor-associated macrophages) of highly immunosuppressive capacities within the TME not only affect oncolysis but also actively impair the functioning of reovirus-driven antitumor T cell immunity. Thus, myeloid cells within the TME play a critical role during the virotherapy, which, if properly understood, can identify novel therapeutic combination strategies potentiating the therapeutic efficacy of reovirus-based cancer therapy.
Topics: Cell Line, Tumor; Clinical Trials as Topic; Humans; Myeloid Cells; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Orthoreovirus; Reoviridae; Tumor Microenvironment
PubMed: 33920168
DOI: 10.3390/v13040654 -
Viruses Aug 2022(MRVs) are increasingly reported to cause various diseases in humans and other animals, with many possibly originating from bats, highlighting the urgent need to...
(MRVs) are increasingly reported to cause various diseases in humans and other animals, with many possibly originating from bats, highlighting the urgent need to investigate the diversity of bat-borne MRVs (BtMRVs). Here, we report the detection and characterization of a reassortant MRV that was isolated from a bat colony in Xinjiang, China. The BtMRV showed a wide host and organ tropism and can efficiently propagate the cell lines of different animals. It caused mild damage in the lungs of the experimentally inoculated suckling mice and was able to replicate in multiple organs for up to three weeks post-inoculation. Complete genome analyses showed that the virus was closely related to MRVs in a wide range of animals. An intricate reassortment network was revealed between the BtMRV and MRVs of human, deer, cattle, civet and other bat species. Specifically, we found a bat-specific clade of segment M1 that provides a gene source for the reassortment of human MRVs. These data provide important insights to understand the diversity of MRVs and their natural circulation between bats, humans, and other animals. Further investigation and surveillance of MRV in bats and other animals are needed to control and prevent potential MRV-related diseases.
Topics: Animals; Cattle; China; Chiroptera; Deer; Humans; Mice; Orthoreovirus; Orthoreovirus, Mammalian; Phylogeny; Sequence Analysis, DNA
PubMed: 36146702
DOI: 10.3390/v14091897 -
Avian Diseases Dec 2022Avian reoviruses are ubiquitous in poultry production worldwide and can be transmitted vertically or horizontally among chickens. The pathogenicity of reoviruses can...
Avian reoviruses are ubiquitous in poultry production worldwide and can be transmitted vertically or horizontally among chickens. The pathogenicity of reoviruses can range from very pathogenic viruses that affect multiple tissues and organs to apathogenic. Avian reoviruses have been associated with many disease presentations, and two of the most economically significant diseases are viral arthritis/tenosynovitis and viral enteritis. Viral arthritis/tenosynovitis has been recognized since the 1950s and essentially disappeared after development of attenuated live and inactivated vaccines in the 1980s but re-emerged in 2011 due to the emergence of antigenic variants. Viral enteritis was first recognized in the 1970s and became the predominant reovirus-associated disease between 2006 and 2011 due to the emergence of pathogenic enterotropic reoviruses. Pathogenicity of reovirus isolates can be evaluated in several ways, including inoculation of day-old broiler chicks with low maternal reovirus antibody titers via the foot pad route or the oral and intratracheal route. Pathogenic reoviruses induce foot pad inflammation within 3 days of inoculation, and more pathogenic reoviruses are able to disseminate to and damage visceral organs. Only reovirus infections in young chickens result in disease due to age-related resistance to disease development. Reoviruses exist as many serotypes and subtypes with various degrees of interrelatedness. The earliest reovirus strains in the United States were antigenically related to each other and are referred to as S1133-like viruses, but in the 2000s, reoviruses emerged that were antigenically different from the S1133-like viruses. Virus neutralization assay using polyclonal antisera has been used to classify the emerging variant reoviruses into serogroups. The first reovirus vaccines were developed in the 1970s, and by the 1980s breeder vaccination programs were established that protected breeders, prevented vertical transmission of reovirus, and provided maternal immunity to the progeny during the crucial first 3 wk of life. With the emergence of antigenic variant reoviruses in the 2000s, vaccination programs using S1133-like vaccines became ineffective. The poultry industry has relied on vaccination with autogenous inactivated reovirus vaccines to alleviate losses due to viral arthritis/tenosynovitis and viral enteritis. Virus isolates used for autogenous vaccines must be updated regularly and are selected based on pathotype, serotype, or Sigma C (σC) genotype. Live attenuated S1133 vaccines are still used in breeder chickens for the priming effect, followed by one or more injections of the inactivated licensed and/or autogenous vaccines. The route of vaccination and the number of doses received by breeder chickens are very important for a sufficient antibody response. Intramuscular vaccination with inactivated vaccines elicits the highest antibody response, while subcutaneous vaccination with inactivated vaccines elicits a low antibody response. More recently, research has focused on development of alternative vaccines and vaccination strategies. An inactivated variant reovirus vaccine was developed that elicits protection against multiple variant serotypes, and experimental recombinant and subunit vaccines have been described and show potential. More research needs to be done to develop better vaccines, vaccination programs, and other control measures for preventing reovirus infection, transmission, and losses due to disease.
Topics: Animals; Orthoreovirus, Avian; Chickens; Tenosynovitis; Virulence; Autovaccines; Viral Vaccines; Poultry Diseases; Poultry; Reoviridae Infections; Arthritis, Infectious; Vaccination; Vaccines, Attenuated; Antibodies, Viral; Vaccines, Inactivated; Enteritis
PubMed: 36715476
DOI: 10.1637/aviandiseases-D-22-99994 -
Viruses Feb 2021De novo viral protein synthesis following entry into host cells is essential for viral replication. As a consequence, viruses have evolved mechanisms to engage the host... (Review)
Review
De novo viral protein synthesis following entry into host cells is essential for viral replication. As a consequence, viruses have evolved mechanisms to engage the host translational machinery while at the same time avoiding or counteracting host defenses that act to repress translation. Mammalian orthoreoviruses are dsRNA-containing viruses whose mRNAs were used as models for early investigations into the mechanisms that underpin the recognition and engagement of eukaryotic mRNAs by host cell ribosomes. However, there remain many unanswered questions and paradoxes regarding translation of reoviral mRNAs in the context of infection. This review summarizes the current state of knowledge about reovirus translation, identifies key unanswered questions, and proposes possible pathways toward a better understanding of reovirus translation.
Topics: Animals; Host-Pathogen Interactions; Humans; Orthoreovirus, Mammalian; Protein Biosynthesis; RNA, Viral; Reoviridae Infections; Ribosomes; Viral Proteins; Virus Replication
PubMed: 33670092
DOI: 10.3390/v13020275 -
Journal of Medical Microbiology Oct 2023Avian reoviruses (ARVs) have a significant economic impact on the poultry industry, affecting commercial and backyard flocks. Spread feco-orally, or vertically, many do...
Avian reoviruses (ARVs) have a significant economic impact on the poultry industry, affecting commercial and backyard flocks. Spread feco-orally, or vertically, many do not cause morbidity, but pathogenic strains can contribute to several diseases, including tenosynovitis/arthritis, which is clinically the most significant. The last decade has seen a surge in cases in the US, and due to ongoing evolution, seven genotypic clusters have now been identified. Control efforts include strict biosecurity and vaccination with commercial and autogenous vaccines. Research priorities include improving understanding of pathogenesis and developing new vaccines guided by ongoing molecular and serologic surveillance.
Topics: Animals; Orthoreovirus, Avian; Chickens; Poultry Diseases; Reoviridae Infections; Phylogeny
PubMed: 37801020
DOI: 10.1099/jmm.0.001761 -
Zoological Research Mar 2024The Chinese tree shrew ( ), a member of the mammalian order Scandentia, exhibits considerable similarities with primates, including humans, in aspects of its nervous,...
The Chinese tree shrew ( ), a member of the mammalian order Scandentia, exhibits considerable similarities with primates, including humans, in aspects of its nervous, immune, and metabolic systems. These similarities have established the tree shrew as a promising experimental model for biomedical research on cancer, infectious diseases, metabolic disorders, and mental health conditions. Herein, we used meta-transcriptomic sequencing to analyze plasma, as well as oral and anal swab samples, from 105 healthy asymptomatic tree shrews to identify the presence of potential zoonotic viruses. In total, eight mammalian viruses with complete genomes were identified, belonging to six viral families, including , , , , , and . Notably, the presence of rotavirus was recorded in tree shrews for the first time. Three viruses - hepacivirus 1, parvovirus, and picornavirus - exhibited low genetic similarity (<70%) with previously reported viruses at the whole-genome scale, indicating novelty. Conversely, three other viruses - hepacivirus 2, hepatovirus A and hepevirus - exhibited high similarity (>94%) to known viral strains. Phylogenetic analyses also revealed that the rotavirus and mammalian orthoreovirus identified in this study may be novel reassortants. These findings provide insights into the diverse viral spectrum present in captive Chinese tree shrews, highlighting the necessity for further research into their potential for cross-species transmission.
Topics: Animals; Phylogeny; Primates; Shrews; Tupaia; Tupaiidae; Viruses
PubMed: 38485510
DOI: 10.24272/j.issn.2095-8137.2023.306 -
Journal of Virology Feb 2022Segmentation of viral genomes provides the potential for genetic exchange within coinfected cells. However, for this potential to be realized, coinfecting genomes must...
Segmentation of viral genomes provides the potential for genetic exchange within coinfected cells. However, for this potential to be realized, coinfecting genomes must mix during the viral life cycle. The efficiency of reassortment, in turn, dictates its potential to drive evolution. The opportunity for mixing within coinfected cells may vary greatly across virus families, such that the evolutionary implications of genome segmentation differ as a result of core features of the viral life cycle. To investigate the relationship between viral replication compartments and genetic exchange, we quantified reassortment in mammalian orthoreovirus (reovirus). Reoviruses carry a 10-segmented, double-stranded RNA genome, which is replicated within proteinaceous structures termed inclusion bodies. We hypothesized that inclusions impose a barrier to reassortment. We quantified reassortment between wild-type () and variant () reoviruses that differ by one nucleotide per segment. Studies of systems in both T1L and T3D backgrounds revealed frequent reassortment without bias toward particular genotypes. However, reassortment was more efficient in the T3D serotype. Since T1L and T3D viruses exhibit different inclusion body morphologies, we tested the impact of this phenotype on reassortment. In both serotypes, reassortment levels did not differ by inclusion morphology. Reasoning that the merging of viral inclusions may be critical for genome mixing, we then tested the effect of blocking merging. Reassortment proceeded efficiently even under these conditions. Our findings indicate that reovirus reassortment is highly efficient despite the localization of many viral processes to inclusion bodies, and that the robustness of this genetic exchange is independent of inclusion body structure and fusion. Quantification of reassortment in diverse viral systems is critical to elucidate the implications of genome segmentation for viral evolution. In principle, genome segmentation offers a facile means of genetic exchange between coinfecting viruses. In practice, there may be physical barriers within the cell that limit the mixing of viral genomes. Here, we tested the hypothesis that localization of the various stages of the mammalian orthoreovirus life cycle within cytoplasmic inclusion bodies compartmentalizes viral replication and limits genetic exchange. Contrary to this hypothesis, our data indicate that reovirus reassortment occurs readily within coinfected cells and is not strongly affected by the structure or dynamics of viral inclusion bodies. We conclude that the potential for reassortment to contribute to reovirus evolution is high.
Topics: Animals; Cell Line; Genome, Viral; Genotype; Inclusion Bodies, Viral; Mice; Microtubules; Orthoreovirus, Mammalian; Reassortant Viruses; Serogroup; Virus Replication
PubMed: 34935439
DOI: 10.1128/JVI.01832-21 -
Poultry Science Oct 2023Since 2005, novel duck reoviruses have been outbreaks in duck breeding areas such as central China and South China. In recent years, the incidence rate of this disease...
Since 2005, novel duck reoviruses have been outbreaks in duck breeding areas such as central China and South China. In recent years, the incidence rate of this disease is still increasing, bringing serious economic losses to waterfowl breeding industry. This study isolated 3 novel duck reoviruses (NDRV-SDLS, NDRV-SDWF, and NDRV-SDYC) from sick ducks in 3 local duck farms in Shandong Province. The study aimed to investigate the characteristics of these viruses. The virus is inoculated into duck embryo fibroblasts, where the virus replicates to produce syncytium and dies within 3 to 5 d. The viruses were also isolated from infected ducks, and RT-PCR amplified the whole genomes after passage purification in duck embryos. The resulting whole genome was analyzed for genetic evolution. The total length of the gene sequencing was 23,418 bp, divided into 10 fragments. Gene sequence comparison showed that the 3 strains had high similarity with novel duck reoviruses (NDRV) but low similarity with chicken-origin reovirus (chicken ARV) and Muscovy duck reovirus (MDRV), especially in the σC segment. Phylogenetic analysis of the 10 fragments showed that the 3 isolates constituted the same evolutionary clade as other DRV reference strains and were far related to ARV and MDRV in different evolutionary clades. The results of all 10 segments indicate that the isolates are in the evolutionary branch of NDRV, suggesting that the novel waterfowl reovirus is the dominant circulating strain in Shandong. This study complements the gene bank information of NDRV and provides references for vaccine research and disease prediction of NDRV in Shandong.
Topics: Animals; Orthoreovirus, Avian; Reoviridae Infections; Phylogeny; Chickens; China; Poultry Diseases
PubMed: 37566967
DOI: 10.1016/j.psj.2023.102969 -
Pathogens (Basel, Switzerland) Nov 2021Piscine orthoreovirus (PRV) infects farmed and wild salmon and trout species in North America, South America, Europe, and East Asia. PRV groups into three distinct...
Piscine orthoreovirus (PRV) infects farmed and wild salmon and trout species in North America, South America, Europe, and East Asia. PRV groups into three distinct genotypes (PRV-1, PRV-2, and PRV-3) that can vary in distribution, host specificity, and/or disease potential. Detection of the virus is currently restricted to genotype specific assays such that surveillance programs require the use of three assays to ensure universal detection of PRV. Consequently, herein, we developed, optimized, and validated a real-time reverse transcription quantitative PCR assay (RT-qPCR) that can detect all known PRV genotypes with high sensitivity and specificity. Targeting a conserved region at the 5' terminus of the M2 segment, the pan-PRV assay reliably detected all PRV genotypes with as few as five copies of RNA. The assay exclusively amplifies PRV and does not cross-react with other salmonid viruses or salmonid host genomes and can be performed as either a one- or two-step RT-qPCR. The assay is highly reproducible and robust, showing 100% agreement in test results from an inter-laboratory comparison between two laboratories in two countries. Overall, as the assay provides a single test to achieve highly sensitive pan-specific PRV detection, it is suitable for research, diagnostic, and surveillance purposes.
PubMed: 34959503
DOI: 10.3390/pathogens10121548 -
Archives of Virology Jul 2022During a surveillance study to monitor porcine epidemic diarrohoea virus and transmissible gastroenteritis virus in India, a total of 1043 swine samples including faeces...
During a surveillance study to monitor porcine epidemic diarrohoea virus and transmissible gastroenteritis virus in India, a total of 1043 swine samples including faeces (n = 264) and clotted blood (n = 779) were collected and tested. Five samples (four faecal and one serum) showed cytopathic effects in Vero cells. Transmission electron microscopy of infectious cell supernatant revealed the presence of two types of virions. Next-generation sequencing (de novo) allowed the complete genome sequence of mammalian orthorubulavirus 5 (MRuV5; 15246 bp) and that of all 10 gene segments of mammalian orthoreovirus to be determined. Genetic analysis of MRuV5 revealed grouping of the Indian MRuV5 with isolates from various mammalian species in South Korea and China, sharing more than 99% nucleotide sequence identity. The deduced amino acid sequences of the HN, NP, and F genes of MRuV5 isolates showed three (92L, 111R, 447H), two (86S, 121S), and two (139T, 246T) amino acid substitutions, respectively, compared to previously reported virus strains. Phylogenic analysis based on S1 gene sequences showed the Indian MRV isolates to be clustered in lineage IV of MRV type 3, with the highest nucleotide sequence identity (97.73%) to MRV3 strain ZJ2013, isolated from pigs in China. The protein encoded by the MRV3 S1 gene was found to contain the amino acid residues 198-204NLAIRLP, 249I, 340D, and 419E, which are known to be involved in sialic acid binding and neurotropism. This is the first report of co-isolation and whole-genomic characterisation of MRuV5 and MRV3 in domestic pigs in India. The present study lays a foundation for further surveillance studies and continuous monitoring of the emergence and spread of evolving viruses that might have pathogenic potential in animal and human hosts.
Topics: Animals; Chlorocebus aethiops; Genomics; Mammalian orthoreovirus 3; Orthoreovirus, Mammalian; Parainfluenza Virus 5; Phylogeny; Reoviridae Infections; Sus scrofa; Swine; Vero Cells
PubMed: 35604502
DOI: 10.1007/s00705-022-05459-x