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Cells Sep 2022Neutrophils are innate leukocytes with diverse effector functions that allow them to respond to pathogens rapidly. Accumulating evidence has highlighted these cells'...
Neutrophils are innate leukocytes with diverse effector functions that allow them to respond to pathogens rapidly. Accumulating evidence has highlighted these cells' complex roles in the host's response to viral infections and tumor progression. Oncolytic virotherapy is emerging as a promising treatment modality in the armamentarium of cancer therapeutics. Oncolytic viruses preferentially kill cancer cells and stimulate tumor-associated inflammation, resulting in tumor regression. Assessing the activity of individual effector cell subsets following oncolytic virotherapy is important in identifying their contribution to antitumor immunity. In this study, we investigated the role of neutrophils in oncolytic Orf-virus-mediated immunotherapy in a murine model of pulmonary melanoma metastases. The systemic administration of the Orf virus stimulated a dramatic increase in the number of leukocytes in circulation and within the tumor microenvironment, most of which were neutrophils. Analysis of tumor-burdened lungs shortly after therapy revealed significant numbers of phenotypically immature neutrophils, with the enhanced expression of molecules affiliated with activation, migration, and cytotoxicity. Neutrophils stimulated by Orf virus therapy were directly tumoricidal through tumor necrosis factor-α-mediated effects and were required for optimal antitumor efficacy following Orf virus therapy. Taken together, these data reveal neutrophils as a crucial innate effector to consider when investigating oncolytic virotherapy.
Topics: Animals; Humans; Immunotherapy; Mice; Neoplasms; Neutrophils; Oncolytic Virotherapy; Oncolytic Viruses; Orf virus; Tumor Microenvironment; Tumor Necrosis Factor-alpha
PubMed: 36139433
DOI: 10.3390/cells11182858 -
Frontiers in Immunology 2022Contagious ecthyma is a highly contagious viral disease with zoonotic significance caused by orf virus (ORFV) that affects domestic, ruminants and humans. Live...
Contagious ecthyma is a highly contagious viral disease with zoonotic significance caused by orf virus (ORFV) that affects domestic, ruminants and humans. Live attenuated virus and attenuated tissue culture vaccines are widely used in the fight against ORFV, however, the conventional attenuated vaccine strains have many drawbacks. The aim of this project was to construct a promising contagious ecthyma vaccine strain with safety, high protection efficacy and accessibility by genetic manipulation to against the disease. Using a natural ORFV-GS14 strain as the parental virus, recombinant virus, rGS14-ΔCBP-ΔGIF, with double deletions in the genes encoding the chemokine binding protein (CBP) and granulocyte/macrophage colony-stimulating factor inhibitory factor (GIF) was generated and characterized and . Results showed that the growth kinetics curve of rGS14-ΔCBP-ΔGIF and parental virus was consistent, both reaching plateau phase at 48 h post infection, which indicated that the double deletion of and genes had little impact on the replication properties of the recombinant virus in primary goat testis (PGT) cell cultures compared with the parental virus. The safety of the double gene-deleted virus was evaluated in lambs. The lambs were monitored for 21 days post infection of the recombinant virus and no ORFV associated symptoms were observed in 21 days post-infection except for slight fever and anorexia in 5 days post-infection, and all lambs inoculated with either recombinant virus or PBS exhibited no clinical signs. To assess the protection efficacy of the rGS14-ΔCBP-ΔGIF, groups of four lambs each were inoculated with rGS14-ΔCBP-ΔGIF, rGS14-ΔCBP, rGS14-ΔGIF or PBS and challenged by a wild type virulent ORFV strain that was isolated from proliferative scabby lesions tissues of infected goat at 21-day post-inoculation. During 14 days post-challenging, lambs inoculated with rGS14-ΔCBP-ΔGIF all remained healthy with unimmunized group all infected, while the single gene-deleted viruses only protected 40% to 50% animals. These results indicated that the double gene-deleted recombinant virus could provide complete protection against virulent ORFV challenging. In conclusion, the double gene-deleted recombinant virus strain, rGS14-ΔCBP-ΔGIF, would be a promising candidate vaccine strains with safety, high protection efficacy and availability.
Topics: Animals; Ecthyma, Contagious; Gene Deletion; Goats; Humans; Macrophage Colony-Stimulating Factor; Male; Orf virus; Sheep; Sheep, Domestic; Vaccines, Attenuated
PubMed: 36119021
DOI: 10.3389/fimmu.2022.961287 -
Open Veterinary Journal 2022Outbreaks of contagious ecthyma (CE) are frequently reported in sheep and goat flocks in Nigeria with severe clinical outcomes. CE is a debilitating and economically...
BACKGROUND
Outbreaks of contagious ecthyma (CE) are frequently reported in sheep and goat flocks in Nigeria with severe clinical outcomes. CE is a debilitating and economically important disease primarily affecting sheep and goats caused by the Orf virus (ORFV). Despite field reports of CE in the country, there is no concise country-wide epidemiological data on the disease and limited genetic data of circulating Nigerian ORFV are available in the public domain.
AIM
An epidemiological survey of CE and molecular characterization of ORFV circulating in Nigeria from 2014 to 2016.
METHOD
Data were collected using designed questionnaires, administered to veterinarians and farmers in selected States of Nigeria. Samples were collected during passive surveillance for CE from 2014 to 2016 which were analyzed by polymerase chain reaction (PCR). The and genes of circulating ORFV were also characterized.
RESULTS
Analysis of the questionnaire showed that 69.54% ( = 82/118) of the farmers claimed to have experienced CE in their flocks with average morbidity and mortality rates of 25% and 15%, respectively. A total of 113 veterinarians participated in the study, with 69.9% ( = 79) familiar with CE and claimed CE causes morbidity rates of 25%-37% and mortality rates of 10%-15% in sheep and goats. Laboratory results revealed that ORFV was detected in 72% (18/25) of outbreak samples analyzed by real-time PCR. Phylogenetic analysis of and genes revealed that Nigerian ORFV sequences belong to clusters I and II and are similar to viruses from India, Ethiopia, and China.
CONCLUSIONS
This study is the first nationwide epidemiological data on the status of CE in sheep and goats in Nigeria. It is also the first report of molecular characterization of two genes of ORFV circulating and causing outbreaks in small ruminants in the country. This study showed that CE is under-reported, widespread and of economic importance to sheep and goat farmers in Nigeria.
Topics: Animals; Ecthyma, Contagious; Goat Diseases; Goats; Nigeria; Orf virus; Phylogeny; Sheep; Sheep Diseases; Surveys and Questionnaires
PubMed: 36118719
DOI: 10.5455/OVJ.2022.v12.i4.18 -
The New Microbiologica Dec 2022Parapoxvirus (PPV) infections are considered neglected zoonoses because their incidence is often unknown or greatly underestimated despite being endemic globally. Here,...
Parapoxvirus (PPV) infections are considered neglected zoonoses because their incidence is often unknown or greatly underestimated despite being endemic globally. Here, we report the comprehensive diagnostic workflow that led to the identification of two cases of persistent PPV infections. The results obtained underline the importance of adopting a "One Health" approach and cross-sectoral collaboration between human and veterinary medicine for precise aetiological diagnosis and correct management of patients affected by zoonotic diseases.
Topics: Animals; Humans; Parapoxvirus; Zoonoses; Poxviridae Infections
PubMed: 36066214
DOI: No ID Found -
Clinical Case Reports Aug 2022Orf is caused by a parapoxvirus. We present a recurrent, giant digital orf case in a female patient with a history of hairy cell leukemia. In spite of shave excision,...
Orf is caused by a parapoxvirus. We present a recurrent, giant digital orf case in a female patient with a history of hairy cell leukemia. In spite of shave excision, the lesion progressed and recurred after digital amputation. Treatment with topical imiquimod cream and systemic subcutaneous interferon alfa-2a was successful.
PubMed: 35999987
DOI: 10.1002/ccr3.6209 -
Tropical Animal Health and Production Aug 2022Orf is an acute, highly contagious, and economically important viral disease of small ruminants. In this study, six orf suspected outbreaks among goats and sheep were...
Orf is an acute, highly contagious, and economically important viral disease of small ruminants. In this study, six orf suspected outbreaks among goats and sheep were investigated from Haryana state and adjoining areas of Rajasthan state during the year 2021. The disease was diagnosed on the basis of clinical signs and molecular identification. The causative agent of the disease, orf virus (ORFV), was confirmed using polymerase chain reaction (PCR) targeting immunodominant envelope antigen (B2L) gene and confirmed by sequencing. The morbidity in goats ranged from 8.75 to 100%, whereas in sheep, it ranged from 0 to 8%. The higher mortality was observed among flocks with mixed infections of orf and peste des petits (PPR) or orf and haemonchosis as compared to other outbreaks. The phylogenetic analysis of sequenced PCR products clustered the current study strains in the same clad with Indian as well as strains from other countries with nucleotide identity more than 99%, signifying a close genetic relationship. The study highlighted the circulation of strains of a single cluster among sheep and goats in Haryana and adjoining areas. Prompt diagnosis of the disease is highly important for facilitating the implementation of control measures to minimize the losses suffered by small and marginal farmers in this region. Further detailed studies are required to delineate the molecular details of ORFV for better understanding the dynamics and molecular epidemiology of strains circulating in the country and for designing the effective vaccines against the disease which are currently lacking in the country.
Topics: Animals; Disease Outbreaks; Goat Diseases; Goats; India; Orf virus; Peste-des-Petits-Ruminants; Peste-des-petits-ruminants virus; Phylogeny; Sheep; Sheep Diseases
PubMed: 35980491
DOI: 10.1007/s11250-022-03269-6 -
Frontiers in Cellular and Infection... 2022Oncolytic viruses have been emerging as a promising therapeutic option for cancer patients, including lung cancer. Orf virus (ORFV), a DNA parapoxvirus, can infect its...
Oncolytic viruses have been emerging as a promising therapeutic option for cancer patients, including lung cancer. Orf virus (ORFV), a DNA parapoxvirus, can infect its natural ungulate hosts and transmit into humans. Moreover, the ORFV has advantages of low toxicity, high targeted, self-amplification and can induce potent Th1-like immunity. This study explored the therapeutic potential of ORFV infection for human lung cancer therapy and investigated the molecular mechanisms. We used a previously described ORFV NA1/11 strain and tested the oncolysis of ORFV NA1/11 in two lines of lung cancer cells and . Treatment of both cell lines with ORFV NA1/11 resulted in a decrease in cell viability by inducing cell cycle arrest in G2/M phase, suppressing cyclin B1 expression and increasing their apoptosis in a caspase-dependent manner. The ORFV NA1/11-infected lung cancer cells were highly immunogenic. Evidently, ORFV NA1/11 infection of lung cancer cells induced oncolysis of tumor cells to release danger-associated molecular patterns, and promoted dendritic cell maturation, and CD8 T cell infiltration in the tumors by enhancing CXCL16 secretion. These findings may help to understand the molecular mechanisms of ORFV oncolysis and aid in the development of novel therapies for lung cancer.
Topics: Animals; Apoptosis; Chemokine CXCL16; Ecthyma, Contagious; Humans; Lung; Lung Neoplasms; Orf virus; Sheep
PubMed: 35959371
DOI: 10.3389/fcimb.2022.910466 -
The Journal of Veterinary Medical... Sep 2022Parapoxvirus (PPV) causes papular stomatitis and contagious pustular dermatitis in ruminants worldwide. The virus is generally transmitted through close contact with...
Parapoxvirus (PPV) causes papular stomatitis and contagious pustular dermatitis in ruminants worldwide. The virus is generally transmitted through close contact with skin lesions containing PPV in infected animals and indirectly through PPV-contaminated materials. PPV-infected animals frequently do not show clinical signs and the route of PPV transmission is sometimes unclear. In this study, the possibility of mechanical transmission of PPV by houseflies (Musca domestica) was investigated using polymerase chain reaction (PCR) gene surveillance. Samples were collected from cattle, sheep, barn environments, direct wash solution of the body surface of houseflies, and indirect wash solution of the body surface and feces of the flies. Bovine papular stomatitis virus, pseudocowpox virus, and orf virus were detected in the oral cavity and body surface of cattle and sheep without clinical signs of PPV infection or barn environments; PPV was considered to have been retained on the farm. PPVs were also detected in the direct wash solution of the body surface of houseflies, and the indirect wash solution of the body surface and feces of the flies. The viral sequence determined from the indirect wash solution of the body surface and feces of the flies was identical to that determined from the body surface of cattle and barns. These results suggested that houseflies may mechanically transmit PPV to both cattle and sheep.
Topics: Animals; Cattle; Cattle Diseases; Farms; Houseflies; Orf virus; Parapoxvirus; Poxviridae Infections; Ruminants; Sheep; Sheep Diseases; Stomatitis
PubMed: 35896345
DOI: 10.1292/jvms.22-0158 -
Viruses Jul 2022Orf virus (ORFV) is distributed worldwide and is the causative agent of contagious ecthyma that mainly occurs in sheep and goats. This disease was reported for the first...
Orf virus (ORFV) is distributed worldwide and is the causative agent of contagious ecthyma that mainly occurs in sheep and goats. This disease was reported for the first time at the end of 18th century in Europe but very little is currently known about the temporal and geographic origins of this virus. In the present study, the use of new Italian whole genomes allowed for better inference on the evolutionary history of ORFV. In accordance with previous studies, two genome types (S and G) were described for infection of sheep and goats, respectively. These two well-differentiated groups of genomes originated for evolutive convergence in the late 1800s in two different areas of the world (Europe for S type and Asia for G type), but it was only in the early 1900s that the effective size of ORFV increased among hosts and the virus spread across the whole European continent. The Italian strains which were sequenced in the present study were isolated on the Mediterranean island of Sardinian and showed to be exclusive to this geographic area. One of them is likely representative of the early European forms of ORFV which infected sheep and became extinct about one century ago. Such an ancient Sardinian strain may have reached the island simple by chance, where it quickly adapted to the new habitat.
Topics: Animals; Ecthyma, Contagious; Goats; Orf virus; Phylogeny; Sheep; Whole Genome Sequencing
PubMed: 35891452
DOI: 10.3390/v14071473 -
Pathogens (Basel, Switzerland) Apr 2022Homologues of interleukin (IL)-10, a pleiotropic immunomodulatory cytokine, have been identified in the genus. The first identified, (ORFV) IL-10, greatly enhanced...
Homologues of interleukin (IL)-10, a pleiotropic immunomodulatory cytokine, have been identified in the genus. The first identified, (ORFV) IL-10, greatly enhanced infection of its host, exhibiting immune modulatory effects equivalent to human IL-10. IL-10-like genes were then identified in (BPSV), (PCPV), (RDPV) and (GSPV). This study aimed to produce and characterise recombinant parapoxvirus IL-10s, then quantitatively compare their receptor binding and immunomodulatory activities. Recombinant IL-10s were expressed, purified, then characterised using bioinformatic, biochemical and enzymatic analyses. Anti-inflammatory effects were assessed in lipoteichoic acid-activated THP-1 monocytes, and stimulatory effects in MC/9 mast cells. IL-10 receptor (IL-10R)1 binding was detected in a competitive displacement assay. BPSV IL-10 inhibited production of monocyte chemoattractant protein (MCP)-1, IL-8 and IL-1β, induced mast cell proliferation, and bound IL-10R1 similarly to ORFV IL-10. PCPV IL-10 showed reduced MCP-1 inhibition, mast cell proliferation, and IL-10R1 binding. RDPV IL-10 displayed reduced inhibition of IL-8 and MCP-1 production. GSPV IL-10 showed limited inhibition of IL-1β production and stimulation of mast cell proliferation. These findings provide valuable insight into IL-10 receptor interactions, and suggest that the parapoxvirus IL-10s play similar pathogenic roles during infection of their hosts.
PubMed: 35631028
DOI: 10.3390/pathogens11050507