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BioEssays : News and Reviews in... Aug 2018Cancer cells seem to exploit mechanisms that evolve as part of physiological tolerance, which is a complementary and often beneficial form of defense. The study of... (Review)
Review
Cancer cells seem to exploit mechanisms that evolve as part of physiological tolerance, which is a complementary and often beneficial form of defense. The study of physiological systems of tolerance can therefore provide insights into the development of a state of host tolerance of cancer, and how to break it. Analysis of these models has the potential to improve our understanding of existing immunological therapeutic targets, and help to identify future targets and rational therapeutic combinations. The treatment of cancer with immune checkpoint inhibitors aims to reverse the progression to tolerance of cancer, and achieve an immunogenic, rather than tolerogenic, homeostasis. Broadening the efficacy and durability of checkpoint inhibitors focuses on reversing tolerance and stimulating immunogenicity in the cancer, host, and environment. Two examples of important physiological states of tolerance that may inform tolerance of cancer are microbial infection and placental reproduction. These states of tolerance result from bilateral shaping of host and non-self, akin to immunoediting in cancer, and offer reliable models to study the immune tolerance paradigm.
Topics: Allografts; Animals; Female; Host-Pathogen Interactions; Humans; Immune Tolerance; Infections; Microbiota; Myxoma virus; Neoplasms; Placenta; Poxviridae Infections; Pregnancy; Tumor Microenvironment
PubMed: 29869436
DOI: 10.1002/bies.201800050 -
Epidemics Sep 2019Many pathogens of conservation concern circulate endemically within natural wildlife reservoir hosts and it is imperative to understand the individual and ecological...
Many pathogens of conservation concern circulate endemically within natural wildlife reservoir hosts and it is imperative to understand the individual and ecological drivers of natural transmission dynamics, if any threat to a related endangered species is to be assessed. Our study highlights the key drivers of infection and shedding dynamics of squirrelpox virus (SQPV) in its reservoir grey squirrel (Sciurus carolinensis) population. To clarify SQPV dynamics in this population, longitudinal data from a 16-month mark-recapture study were analysed, combining serology with real-time quantitative PCR to identify periods of acute viraemia and chronic viral shedding. At the population level, we found SQPV infection prevalence, viral load and shedding varied seasonally, peaking in autumn and early spring. Individually, SQPV was shown to be a chronic infection in >80% of grey squirrels, with viral loads persisting over time and bouts of potential recrudescence or reinfection occurring. A key recurring factor significantly associated with SQPV infection risk was the presence of co-infecting squirrel adenovirus (ADV). In dual infected squirrels, longitudinal analysis showed that prior ADV viraemia increased the subsequent SQPV load in the blood. However, there was a strong, negative association between prior ADV viraemia and subsequent SQPV shedding from the forearm, probably caused by ADV prolonging the SQPV acute viraemic phase, so delaying onset of the chronic shedding phase, and thereby altering viral shedding patterns over the time scales examined here. Hence, co-circulating ADV infection may be involved in mediating both the quantitative levels of SQPV infection and the timing and degree of subsequent infectiousness of grey squirrels.
Topics: Animals; Poxviridae Infections; Prevalence; Sciuridae; Seasons; Viral Load
PubMed: 31327730
DOI: 10.1016/j.epidem.2019.100352 -
Preventive Veterinary Medicine Nov 2021Sheeppox and goatpox (SGP) are transboundary, highly contagious diseases affecting sheep and goats with characteristic clinical signs. SGP affect populations of small...
Sheeppox and goatpox (SGP) are transboundary, highly contagious diseases affecting sheep and goats with characteristic clinical signs. SGP affect populations of small ruminants in Africa, Asia and the Middle East and, as a result, threaten farmers' livelihoods. Despite their importance, studies looking at factors that increase the risk of sheeppox-virus (SPPV) and goatpox-virus (GTPV) exposure and infection are limited. A cross-sectional study was conducted in three states of Northern Nigeria (Bauchi, Kaduna and Plateau) to determine the sero-prevalence and spatial patterns of SGP, and identify risk factors for SPPV/GTPV exposure at animal and household level. Sera samples were collected from 1,800 small ruminants from 300 households. Data on putative risk factors were collected using a standardised questionnaire. Twenty-nine small ruminants were sero-positive to SGP - apparent weighted sero-prevalence 2.0 %; 95 % C.I. 1.1-.3.0 %. Sero-positive animals came from 19 (6.3 %) households. Analysis of the questionnaire showed that a fifth (20.3 %) of farmers claimed to have experienced SGP outbreaks previously in their flocks, with 33 (1.8 %) of the individual animals sampled in this study reported to have had clinical signs. At animal level, the odds of being sero-positive were higher in older animals (>24months; OR = 8.0, p = 0.008 vs ≤24 months) and small ruminants with a history of clinical SGP (OR = 16.9, p = 0.01). Bringing new small ruminants into the household and having a history of SGP in the flock were the main factors identified at household level. Households were less likely to be sero-positive if the time between bringing animals into the household and sampling was over a year (PR = 0.31, p = 0.05), while households with a history of SGP were more likely to be sero-positive regardless of the timeframe. Important spatial heterogeneity was found. The Bayes smooth rate ranged from 0.06 to 4.10 % across local government areas (LGA), with LGA in the north-east or north-west of the study area identified as hot-spots for SGP exposure. Results from this study shed new light on the understanding of SGP epidemiology and provide key inputs to design risk-based surveillance and intervention programmes in the area.
Topics: Animals; Bayes Theorem; Capripoxvirus; Cross-Sectional Studies; Goat Diseases; Goats; Nigeria; Poxviridae Infections; Prevalence; Sheep; Sheep Diseases
PubMed: 34479042
DOI: 10.1016/j.prevetmed.2021.105473 -
BMC Veterinary Research Oct 2023Sheep and goat pox (SGP) caused by sheep poxvirus (SPV) and goat poxvirus (GPV) respectively; are transboundary and World Organisation for Animal Health...
BACKGROUND
Sheep and goat pox (SGP) caused by sheep poxvirus (SPV) and goat poxvirus (GPV) respectively; are transboundary and World Organisation for Animal Health (WOAH)-notifiable viral diseases. There is barely any coherent information about the distribution and prevalence of SGP for Uganda. We therefore conducted this study to describe the temporal and spatial distribution of SGP suspected outbreaks in Uganda for the period 2011-2020 as well as serologically confirm presence of SGP antibodies in suspected SGP outbreaks reported in 2021-2022.
RESULTS
Thirty-seven [37] SGP outbreaks were reported across the country during the study period. North-eastern region [that comprises of Karamoja region] had the highest number of outbreaks [n = 17, 45%]; followed by Central [n = 9, 2.4%], Northern [n = 8, 2.2%] and Western region [n = 3, 0.08%]. Reports from district veterinary personnel indicate that the prevalence of; and mortality rate and case fatality rate associated with SGP were 0.06%, 0.02% and 32% respectively. There was a steady increase in the number of reported SGP outbreaks [x̄ = 4] over the study period. Seropositivity of SGPV antibodies in outbreak sheep and goats that were investigated during the study period [2021-2022] was [n = 41, 27%, 95 CI;] CONCLUSION: Our analyses of SGPV passive and active reports indicate that SGP is present in Uganda with a decade long average of four outbreaks per annum. During this period, about a third of all SGPV-clinically infected animals died. SPG is therefore a major constraint to small ruminant health and productivity in Uganda. Introduction of animals from infected herds and breach in farm biosecurity were the most important predictors of SGP outbreaks. In addition to the already existing SGP commercial vaccines, small ruminant screening for SGPV before introducing them to naïve herds and ensuring on farm biosecurity should be part of the SGP control tool pack for Ugandan small ruminant farmers.
Topics: Sheep; Animals; Uganda; Goat Diseases; Sheep Diseases; Poxviridae Infections; Capripoxvirus; Goats; Disease Outbreaks; Spatio-Temporal Analysis
PubMed: 37891597
DOI: 10.1186/s12917-023-03788-w -
Viruses Sep 2020Capripox viruses, with their members "lumpy skin disease virus (LSDV)", "goatpox virus (GTPV)" and "sheeppox virus (SPPV)", are described as the most serious pox...
Capripox viruses, with their members "lumpy skin disease virus (LSDV)", "goatpox virus (GTPV)" and "sheeppox virus (SPPV)", are described as the most serious pox diseases of production animals. A GTPV isolate and a SPPV isolate were sequenced in a combined approach using nanopore MinION sequencing to obtain long reads and Illumina high throughput sequencing for short precise reads to gain full-length high-quality genome sequences. Concomitantly, sheep and goats were inoculated with SPPV and GTPV strains, respectively. During the animal trial, varying infection routes were compared: a combined intravenous and subcutaneous infection, an only intranasal infection, and the contact infection between naïve and inoculated animals. Sheep inoculated with SPPV showed no clinical signs, only a very small number of genome-positive samples and a low-level antibody reaction. In contrast, all GTPV inoculated or in-contact goats developed severe clinical signs with high viral genome loads observed in all tested matrices. Furthermore, seroconversion was detected in nearly all goats and no differences concerning the severity of the disease depending on the inoculation route were observed. Conclusively, the employed SPPV strain has the properties of an attenuated vaccine strain, consistent with the genetic data, whereas the GTPV strain represents a highly virulent field strain.
Topics: Animals; Capripoxvirus; DNA, Viral; Female; Genome, Viral; Goat Diseases; Goats; Male; Phylogeny; Poxviridae Infections; Ruminants; Sheep; Sheep Diseases; Vaccines, Attenuated
PubMed: 32998423
DOI: 10.3390/v12101098 -
Journal of Virology Feb 2017Myxomatosis is a recurrent problem on rabbit farms throughout Europe despite the success of vaccines. To identify gene variations of field and vaccine strains that may...
UNLABELLED
Myxomatosis is a recurrent problem on rabbit farms throughout Europe despite the success of vaccines. To identify gene variations of field and vaccine strains that may be responsible for changes in virulence, immunomodulation, and immunoprotection, the genomes of 6 myxoma virus (MYXV) strains were sequenced: German field isolates Munich-1, FLI-H, 2604, and 3207; vaccine strain MAV; and challenge strain ZA. The analyzed genomes ranged from 147.6 kb (strain MAV) to 161.8 kb (strain 3207). All sequences were affected by several mutations, covering 24 to 93 open reading frames (ORFs) and resulted in amino acid substitutions, insertions, or deletions. Only strains Munich-1 and MAV revealed the deletion of 10 ORFs (M007L to M015L) and 11 ORFs (M007L to M008.1L and M149R to M008.1R), respectively. Major differences were observed in the 27 immunomodulatory proteins encoded by MYXV. Compared to the reference strain Lausanne, strains FLI-H, 2604, 3207, and ZA showed the highest amino acid identity (>98.4%). In strains Munich-1 and MAV, deletion of 5 and 10 ORFs, respectively, was observed, encoding immunomodulatory proteins with ankyrin repeats or members of the family of serine protease inhibitors. Furthermore, putative immunodominant surface proteins with homology to vaccinia virus (VACV) were investigated in the sequenced strains. Only strain MAV revealed above-average frequencies of amino acid substitutions and frameshift mutations. Finally, we performed recombination analysis and found signs of recombination in vaccine strain MAV. Phylogenetic analysis showed a close relationship of strain MAV and the MSW strain of Californian MYXV. However, in a challenge model, strain MAV provided full protection against lethal challenges with strain ZA.
IMPORTANCE
Myxoma virus (MYXV) is pathogenic for European rabbits and two North American species. Due to sophisticated strategies in immune evasion and oncolysis, MYXV is an important model virus for immunological and pathological research. In its natural hosts, MYXV causes a benign infection, whereas in European rabbits, it causes the lethal disease myxomatosis. Since the introduction of MYXV into Australia and Europe for the biological control of European rabbits in the 1950s, a coevolution of host and pathogen has started, selecting for attenuated virus strains and increased resistance in rabbits. Evolution of viruses is a continuous process and influences the protective potential of vaccines. In our analyses, we sequenced 6 MYXV field, challenge, and vaccine strains. We focused on genes encoding proteins involved in virulence, host range, immunomodulation, and envelope composition. Genes affected most by mutations play a role in immunomodulation. However, attenuation cannot be linked to individual mutations or gene disruptions.
Topics: Amino Acid Substitution; Animals; Ankyrin Repeat; Apoptosis; Cell Line; Chlorocebus aethiops; Evolution, Molecular; Genetic Variation; Genome, Viral; Genomics; Immunomodulation; Inflammation; Leukocytes; Mutation; Myxoma virus; Open Reading Frames; Phylogeny; Poxviridae Infections; Protein Binding; Protein Interaction Mapping; Rabbits; Receptors, Immunologic; Viral Proteins; Viral Vaccines
PubMed: 27903800
DOI: 10.1128/JVI.01570-16 -
Virologica Sinica Apr 2024The persistent epidemic of human mpox, caused by mpox virus (MPXV), raises concerns about the future spread of MPXV and other poxviruses. MPXV is a typical zoonotic... (Review)
Review
The persistent epidemic of human mpox, caused by mpox virus (MPXV), raises concerns about the future spread of MPXV and other poxviruses. MPXV is a typical zoonotic virus which can infect human and cause smallpox-like symptoms. MPXV belongs to the Poxviridae family, which has a relatively broad host range from arthropods to vertebrates. Cross-species transmission of poxviruses among different hosts has been frequently reported and resulted in numerous epidemics. Poxviruses have a complex linear double-strand DNA genome that encodes hundreds of proteins. Genes related to the host range of poxvirus are called host range genes (HRGs). This review briefly introduces the taxonomy, phylogeny and hosts of poxviruses, and then comprehensively summarizes the current knowledge about the cross-species transmission of poxviruses. In particular, the HRGs of poxvirus are described and their impacts on viral host range are discussed in depth. We hope that this review will provide a comprehensive perspective about the current progress of researches on cross-species transmission and HRG variation of poxviruses, serving as a valuable reference for academic studies and disease control in the future.
Topics: Host Specificity; Animals; Humans; Poxviridae Infections; Poxviridae; Phylogeny; Genome, Viral
PubMed: 38272237
DOI: 10.1016/j.virs.2024.01.007 -
Viruses Mar 2018Diagnostic electron microscopy (DEM) was an essential component of viral diagnosis until the development of highly sensitive nucleic acid amplification techniques (NAT).... (Review)
Review
Diagnostic electron microscopy (DEM) was an essential component of viral diagnosis until the development of highly sensitive nucleic acid amplification techniques (NAT). The simple negative staining technique of DEM was applied widely to smallpox diagnosis until the world-wide eradication of the human-specific pathogen in 1980. Since then, the threat of smallpox re-emerging through laboratory escape, molecular manipulation, synthetic biology or bioterrorism has not totally disappeared and would be a major problem in an unvaccinated population. Other animal poxviruses may also emerge as human pathogens. With its rapid results (only a few minutes after arrival of the specimen), no requirement for specific reagents and its "open view", DEM remains an important component of virus diagnosis, particularly because it can easily and reliably distinguish smallpox virus or any other member of the orthopoxvirus (OPV) genus from parapoxviruses (PPV) and the far more common and less serious herpesviruses (herpes simplex and varicella zoster). Preparation, enrichment, examination, internal standards and suitable organisations are discussed to make clear its continuing value as a diagnostic technique.
Topics: Animals; Exanthema; Herpesviridae; Herpesviridae Infections; Humans; Microscopy, Electron; Orthopoxvirus; Poxviridae Infections; Smallpox
PubMed: 29565285
DOI: 10.3390/v10040142 -
Expert Review of Anti-infective Therapy Mar 2021Tecovirimat (TPOXX®; ST-246) was approved for the treatment of symptomatic smallpox by the USFDA in July of 2018 and has been stockpiled by the US government for use in... (Review)
Review
INTRODUCTION
Tecovirimat (TPOXX®; ST-246) was approved for the treatment of symptomatic smallpox by the USFDA in July of 2018 and has been stockpiled by the US government for use in a smallpox outbreak. While there has not been a reported case of smallpox since 1978 it is still considered a serious bioterrorism threat.
AREAS COVERED
A brief history of smallpox from its proposed origins as a human disease through its eradication in the late 20th century is presented. The current smallpox threat and the current public health response plans are described. The discovery, and development of tecovirimat through NDA submission and subsequent approval for treatment of smallpox are discussed. Google Scholar and PubMed were searched over all available dates for relevant publications.
EXPERT OPINION
Approval of tecovirimat to treat smallpox represents an important milestone in biosecurity preparedness. Incorporating tecovirimat into the CDC smallpox response plan, development of pediatric liquid and intravenous formulations, and approval for post-exposure prophylaxis would provide additional health security benefit.Tecovirimat shows broad efficacy against orthopoxviruses in vitro and in vivo and could be developed for use against emerging orthopoxvirus diseases such as monkeypox, vaccination-associated adverse events, and side effects of vaccinia oncolytic virus therapy.
Topics: Antiviral Agents; Benzamides; Bioterrorism; Humans; Isoindoles; Orthopoxvirus; Poxviridae Infections; Smallpox
PubMed: 32882158
DOI: 10.1080/14787210.2020.1819791 -
Skin Research and Technology : Official... Oct 2023Poxviruses belong to the Poxviridae family, a group of pathogens known for their high infectivity in humans, posing significant health threats. One of the most... (Review)
Review
Poxviruses belong to the Poxviridae family, a group of pathogens known for their high infectivity in humans, posing significant health threats. One of the most well-known representatives of poxvirus infections is smallpox, which has been successfully eradicated. However, in recent years, there has been a resurgence in cases of mpox, another member of the Poxviridae family, raising concerns about the potential for a global pandemic or a worldwide health crisis. While the typical clinical presentation of mpox and other poxvirus infections often involves cutaneous lesions, there have been reports of various atypical and non-classic clinical manifestations. Dermoscopy has emerged as a crucial diagnostic tool, aiding dermatologists in clinical practice to make informed decisions. In this summary, we provide an overview of the clinical and dermoscopic features of representative cutaneous lesions associated with human poxvirus infections, including mpox, orf, milker's nodule, and molluscum contagiosum.
Topics: Humans; Mpox (monkeypox); Dermoscopy; Poxviridae Infections; Poxviridae
PubMed: 37881051
DOI: 10.1111/srt.13489