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Viruses Aug 2014Maturation is an intrinsic phase of the viral life cycle and is often intertwined with egress. In this review we focus on orbivirus maturation by using Bluetongue virus... (Review)
Review
Maturation is an intrinsic phase of the viral life cycle and is often intertwined with egress. In this review we focus on orbivirus maturation by using Bluetongue virus (BTV) as a representative. BTV, a member of the genus Orbivirus within the family Reoviridae, has over the last three decades been subjected to intense molecular study and is thus one of the best understood viruses. BTV is a non-enveloped virus comprised of two concentric protein shells that encapsidate 10 double-stranded RNA genome segments. Upon cell entry, the outer capsid is shed, releasing the core which does not disassemble into the cytoplasm. The polymerase complex within the core then synthesizes transcripts from each genome segment and extrudes these into the cytoplasm where they act as templates for protein synthesis. Newly synthesized ssRNA then associates with the replicase complex prior to encapsidation by inner and outer protein layers of core within virus-triggered inclusion bodies. Maturation of core occurs outside these inclusion bodies (IBs) via the addition of the outer capsid proteins, which appears to be coupled to a non-lytic, exocytic pathway during early infection. Similar to the enveloped viruses, BTV hijacks the exocytosis and endosomal sorting complex required for trafficking (ESCRT) pathway via a non-structural glycoprotein. This exquisitely detailed understanding is assembled from a broad array of assays, spanning numerous and diverse in vitro and in vivo studies. Presented here are the detailed insights of BTV maturation and egress.
Topics: Biological Transport; Bluetongue virus; Capsid; Exocytosis; Inclusion Bodies, Viral; Virus Assembly; Virus Release
PubMed: 25196482
DOI: 10.3390/v6083250 -
Current Opinion in Virology Oct 2020Bluetongue virus (BTV) reverse genetics (RG), available since 2007, has allowed the dissection of the virus replication cycle, including discovery of a primary... (Review)
Review
Bluetongue virus (BTV) reverse genetics (RG), available since 2007, has allowed the dissection of the virus replication cycle, including discovery of a primary replication stage. This information has allowed the generation of Entry-Competent-Replication-Abortive (ECRA) vaccines, which enter cells and complete primary replication but fail to complete the later stage. A series of vaccine trials in sheep and cattle either with a single ECRA serotype or a cocktail of multiple ECRA serotypes have demonstrated that these vaccines provide complete protection against virulent virus challenge without cross-serotype interference. Similarly, an RG system developed for the related African Horse Sickness virus, which causes high mortality in equids has provided AHSV ECRA vaccines that are protective in horses. ECRA vaccines were incapable of productive replication in animals despite being competent for cell entry. This technology allows rapid generation of emerging Orbivirus vaccines and offers immunogenicity and safety levels that surpass attenuated or recombinant routes.
Topics: Animals; Antibodies, Neutralizing; Antibodies, Viral; Bluetongue; Bluetongue virus; Cattle; Orbivirus; Reoviridae Infections; Reverse Genetics; Sheep; Vaccines, Attenuated; Viral Vaccines; Virus Replication
PubMed: 32610251
DOI: 10.1016/j.coviro.2020.05.003 -
Viruses Aug 2023Midges are widely distributed globally and can transmit various human and animal diseases through blood-sucking. As part of this study, 259,300 midges were collected...
Midges are widely distributed globally and can transmit various human and animal diseases through blood-sucking. As part of this study, 259,300 midges were collected from four districts in Yunnan province, China, to detect the viral richness and diversity using metavirome analysis techniques. As many as 26 virus families were detected, and the partial sequences of bluetongue virus (BTV), dengue virus (DENV), and Getah virus (GETV) were identified by phylogenetic analysis and PCR amplification. Two BTV gene fragments, 866 bps for the VP2 gene of BTV type 16 and 655 bps for the VP5 gene of BTV type 21, were amplified. The nucleotide sequence identities of the two amplified BTV fragments were 94.46% and 98.81%, respectively, with two classical BTV-16 (GenBank: JN671907) and BTV-21 strains (GenBank: MK250961) isolated in Yunnan province. Furthermore, the BTV-16 DH2021 strain was successfully isolated in C6/36 cells, and the peak value of the copy number reached 3.13 × 10 copies/μL after five consecutive BHK-21 cell passages. Moreover, two 2054 bps fragments including the E gene of DENV genotype Asia II were amplified and shared the highest identity with the DENV strain isolated in New Guinea in 1944. A length of 656 bps GETV gene sequence encoded the partial capsid protein, and it shared the highest identity of 99.68% with the GETV isolated from Shandong province, China, in 2017. Overall, this study emphasizes the importance of implementing prevention and control strategies for viral diseases transmitted by midges in China.
Topics: Animals; Humans; China; Phylogeny; Alphavirus; Asia; Capsid Proteins; Bluetongue virus
PubMed: 37766224
DOI: 10.3390/v15091817 -
Transboundary and Emerging Diseases Nov 2022Tibet orbivirus (TIBOV), a new candidate of Orbivirus genus, was initially isolated from mosquitoes in Tibet in 2009 and subsequently from both Culicoides and mosquitoes...
Tibet orbivirus (TIBOV), a new candidate of Orbivirus genus, was initially isolated from mosquitoes in Tibet in 2009 and subsequently from both Culicoides and mosquitoes in several provinces of China and Japan. Little is known about the origin, genetic diversity, dissemination and pathogenicity of TIBOV, although its potential threat to animal health has been acknowledged. In this study, two viruses, V290/YNSZ and V298/YNJH, were isolated from the Culicoides and sentinel cattle in Yunnan Province. Their genome sequences, cell tropism in mammalian and insect cell lines along with pathogenicity in suckling mice were determined. Genome phylogenetic analyses confirmed their classification as TIBOV species; however, OC1 proteins of the V290/YNSZ and V298/YNJH shared maximum sequence identities of 31.5% and 33.9% with other recognized TIBOV serotypes (TIBOV-1 to TIBOV-4) and formed two monophyletic branches in phylogenetic tree, indicating they represented two novel TIBOV serotypes which were tentatively designated as TIBOV-5 and TIBOV-6. The viruses replicated robustly in BHK, Vero and C6/36 cells and triggered overt clinical symptoms in suckling mice after intracerebral inoculation, causing mortality of 100% and 25%. Cross-sectional epidemiology analysis revealed silent circulation of TIBOV in Yunnan Province with overall prevalence of 16.4% (18/110) in cattle, 10.8% (13/120) in goats and 5.5% (6/110) in swine. The prevalence patterns of four investigated TIBOV serotypes (TIBOV-1, -2, -5 and 6) differed from each one another, with their positive rates ranging from 8.2% (9/110) for TIBOV-2 in cattle to 0.9% (1/110) for TIBOV-1 and TIBOV-5 in cattle and swine. Our findings provided new insights for diversity, pathogenicity and epidemiology of TIBOV and formed a basis for future studies addressing the geographical distribution and the zoonotic potential of TIBOV.
Topics: Cattle; Animals; Mice; Swine; China; Tibet; Ceratopogonidae; Phylogeny; Cross-Sectional Studies; Serogroup; Orbivirus; Goats
PubMed: 36047657
DOI: 10.1111/tbed.14691 -
Viruses Nov 2021Epizootic hemorrhagic disease (EHD) is an insect-transmitted viral disease of wild and domestic ruminants. It was first described following a 1955 epizootic in North... (Review)
Review
Epizootic hemorrhagic disease (EHD) is an insect-transmitted viral disease of wild and domestic ruminants. It was first described following a 1955 epizootic in North American white-tailed deer (), a species which is highly susceptible to the causative agent of EHD, epizootic hemorrhagic disease virus (EHDV). EHDV has been detected globally across tropical and temperate regions, largely corresponding to the presence of spp. biting midges which transmit the virus between ruminant hosts. It regularly causes high morbidity and mortality in wild and captive deer populations in endemic areas during epizootics. Although cattle historically have been less susceptible to EHDV, reports of clinical disease in cattle have increased in the past two decades. There is a pressing need to identify new methods to prevent and mitigate outbreaks and reduce the considerable impacts of EHDV on livestock and wildlife. This review discusses recent research advancements towards the control of EHDV, including the development of new investigative tools and progress in basic and applied research focused on virus detection, disease mitigation, and vector control. The potential impacts and implications of these advancements on EHD management are also discussed.
Topics: Animals; Cattle; Ceratopogonidae; Deer; Disease Outbreaks; Hemorrhagic Disease Virus, Epizootic; Insect Control; Insect Vectors; Reoviridae Infections; Serogroup
PubMed: 34835074
DOI: 10.3390/v13112268 -
Revue Scientifique Et Technique... Jun 2021The availability of rapid, highly sensitive and specific molecular and serologic diagnostic assays, such as competitive enzyme-linked immunosorbent assay (cELISA), has... (Review)
Review
The availability of rapid, highly sensitive and specific molecular and serologic diagnostic assays, such as competitive enzyme-linked immunosorbent assay (cELISA), has expedited the diagnosis of emerging transboundary animal diseases, including bluetongue (BT) and African horse sickness (AHS), and facilitated more thorough characterisation of their epidemiology. The development of assays based on real-time, reverse-transcription polymerase chain reaction (RT-PCR) to detect and identify the numerous serotypes of BT virus (BTV) and AHS virus (AHSV) has aided in-depth studies of the epidemiology of BTV infection in California and AHSV infection in South Africa. The subsequent evaluation of pan-serotype, real-time, RT-PCR-positive samples through the use of serotype-specific RT-PCR assays allows the rapid identification of virus serotypes, reducing the need for expensive and time-consuming conventional methods, such as virus isolation and serotype-specific virus neutralisation assays. These molecular assays and cELISA platforms provide tools that have enhanced epidemiologic surveillance strategies and improved our understanding of potentially altered Culicoides midge behaviour when infected with BTV. They have also supported the detection of subclinical AHSV infection of vaccinated horses in South Africa. Moreover, in conjunction with whole genome sequence analysis, these tests have clarified that the mechanism behind recent outbreaks of AHS in the AHS-controlled area of South Africa was the result of the reversion to virulence and/or genome reassortment of live attenuated vaccine viruses. This review focuses on the use of contemporary molecular diagnostic assays in the context of recent epidemiologic studies and explores their advantages over historic virus isolation and serologic techniques.
Topics: African Horse Sickness; African Horse Sickness Virus; Animals; Animals, Wild; Bluetongue virus; Horse Diseases; Horses; South Africa
PubMed: 34140737
DOI: 10.20506/rst.40.1.3211 -
Current Opinion in Virology Dec 2017Congenital infections of domestic animals with viruses in several families, including Bunyaviridae, Flaviridae, Parvoviridae, and Reoviridae, are the cause of naturally... (Review)
Review
Congenital infections of domestic animals with viruses in several families, including Bunyaviridae, Flaviridae, Parvoviridae, and Reoviridae, are the cause of naturally occurring teratogenic central nervous system and/or musculoskeletal defects (arthrogryposis) in domestic animals. Congenital infections of ruminant livestock with bluetongue virus (BTV) and some related members of the genus Orbivirus (family Reoviridae) have clearly shown the critical role of gestational age at infection in determining outcome. Specifically, fetuses infected prior to mid-gestation that survive congenital BTV infection are born with cavitating central nervous system defects that range from severe hydranencephaly to cerebral cysts (porencephaly). Generally, the younger the fetus (in terms of gestational age) at infection, the more severe the teratogenic lesion at birth. Age-dependent virus infection and destruction of neuronal and/or glial cell precursors that populate the developing central nervous system are responsible for these naturally occurring virus-induced congenital defects of animals, thus lesions are most severe when progenitor cells are infected prior to their normal migration during embryogenesis. Whereas congenital infection is characteristic of certain BTV strains, notably live-attenuated (modified-live) vaccine viruses that have been passaged in embryonating eggs, transplacental transmission is not characteristic of many field strains of the virus and much remains to be determined regarding the genetic determinants of transplacental transmission of individual virus strains.
Topics: Age Factors; Animals; Bluetongue; Bluetongue virus; Congenital Abnormalities; Female; Gestational Age; Infectious Disease Transmission, Vertical; Livestock; Orbivirus; Pregnancy; Reoviridae Infections; Ruminants; Sheep; Teratogens; Virus Diseases
PubMed: 29107849
DOI: 10.1016/j.coviro.2017.10.002 -
Frontiers in Immunology 2023Bluetongue virus (BTV) is an arbovirus transmitted by the bite of infected midges that affects domestic and wild ruminants producing great economic losses. The...
Bluetongue virus (BTV) is an arbovirus transmitted by the bite of infected midges that affects domestic and wild ruminants producing great economic losses. The infection induces an IFN response, followed by an adaptive immune response that is essential in disease clearance. BTV can nonetheless impair IFN and humoral responses. The main goal of this study was to gain a more detailed understanding of BTV pathogenesis and its effects on immune cell populations. To this end, we combined flow cytometry and transcriptomic analyses of several immune cells at different times post-infection (pi). Four sheep were infected with BTV serotype 8 and blood samples collected at days 0, 3, 7 and 15pi to perform transcriptomic analysis of B-cell marker, CD4, CD8, and CD14 sorted peripheral mononuclear cells. The maximum number of differentially expressed genes occurred at day 7pi, which coincided with the peak of infection. KEGG pathway enrichment analysis indicated that genes belonging to virus sensing and immune response initiation pathways were enriched at day 3 and 7 pi in all 4 cell population analyzed. Transcriptomic analysis also showed that at day 7pi T cell exhaustion pathway was enriched in CD4 cells, while CD8 cells downregulated immune response initiation pathways. T cell functional studies demonstrated that BTV produced an acute inhibition of CD4 and CD8 T cell activation at the peak of replication. This coincided with PD-L1 upregulation on the surface of CD4 and CD8 T cells as well as monocytes. Taken together, these data indicate that BTV could exploit the PD1/PD-L1 immune checkpoint to impair T cell responses. These findings identify several mechanisms in the interaction between host and BTV, which could help develop better tools to combat the disease.
Topics: Sheep; Animals; CD8-Positive T-Lymphocytes; B7-H1 Antigen; CD4-Positive T-Lymphocytes; Bluetongue virus; Immunosuppression Therapy
PubMed: 37920474
DOI: 10.3389/fimmu.2023.1255803 -
The Journal of General Virology Sep 2021The genus includes a variety of pathogenic viruses that are transmitted by biting midges, mosquitoes and ticks. Some of the economically most relevant orbiviruses are...
The genus includes a variety of pathogenic viruses that are transmitted by biting midges, mosquitoes and ticks. Some of the economically most relevant orbiviruses are endemic to Namibia, like the livestock-pathogenic Bluetongue and African horse sickness viruses. Here, we assessed the diversity of orbiviruses circulating in the Zambezi region of north-eastern Namibia. A total of 10 250 biting midges and 10 206 mosquitoes were collected and screened for orbivirus infections. We identified Palyam virus (PALV) in a pool of biting midges ( sp.) sampled in the Wuparo Conservancy and three strains of Corriparta virus (CORV) in sp. mosquitoes sampled in Mudumu National Park and the Mashi Conservancy. This is, to our knowledge, the first detection of PALV and CORV in Namibia. Both viruses infect vertebrates but only PALV has been reported to cause disease. PALV can cause foetal malformations and abortions in ruminants. Furthermore, a novel orbivirus, related to Kammavanpettai virus from India and Umatilla virus from North America, was discovered in biting midges ( sp.) originating from Mudumu National Park and tentatively named Mudumu virus (MUMUV). Complete genomes of PALV, CORV and MUMUV were sequenced and genetically characterized. The Namibian CORV strain showed 24.3 % nucleotide divergence in its subcore shell gene to CORV strains from Australia, indicating that African CORV variants vary widely from their Australian relatives. CORV was isolated in cell culture and replicated to high titres in mosquito and duck cells. No growth was found in rodent and primate cells. The data presented here show that diverse orbiviruses are endemic to the Zambezi region. Further studies are needed to assess their effects on wildlife and livestock.
Topics: Animals; Cell Line; Ceratopogonidae; Culicidae; Genome, Viral; High-Throughput Nucleotide Sequencing; Insect Vectors; Mosquito Vectors; Namibia; Orbivirus; Phylogeny; Virus Replication; Whole Genome Sequencing
PubMed: 34554079
DOI: 10.1099/jgv.0.001662 -
The Veterinary Record Nov 2021
Topics: Animals; Bluetongue; Bluetongue virus; Cattle; Cattle Diseases; Sentinel Surveillance; Sheep; Sheep Diseases
PubMed: 34739108
DOI: 10.1002/vetr.1151