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Journal of Medical Virology Jan 2023A multicountry outbreak of the monkeypox virus has gained global attention. As of May 25, 250 confirmed human monkeypox cases have been reported globally. Monkeypox is...
A multicountry outbreak of the monkeypox virus has gained global attention. As of May 25, 250 confirmed human monkeypox cases have been reported globally. Monkeypox is caused by the Monkeypox virus, which belongs to the Orthopoxvirus genus and Poxviridae family. Monkeypox is often a self-limiting infection, with symptoms lasting 2-4 weeks with the case fatality ratio around 3%-6%. Monkeypox is transmitted to humans by direct contact with an infected person or animal or contact with virus-contaminated material. Human monkeypox infections may lead to various medical complications such as fever, rash, and lymphadenopathies. Pneumonitis, encephalitis, sight-threatening keratitis, and subsequent bacterial infections are all possible complications of monkeypox. An antiviral agent developed to treat smallpox has also been approved for use in the treatment of monkeypox in the United States. Vaccines used in the smallpox eradication program also provided immunity to monkeypox. Newer vaccines have been developed, one of which has been approved for monkeypox prevention. In this study, we provide information about the recent outbreaks of human monkeypox, epidemiology, transmission pattern, possible diagnosis techniques, therapeutics, and available preventive strategies.
Topics: Animals; Humans; United States; Mpox (monkeypox); Smallpox; Monkeypox virus; Public Health; Disease Outbreaks
PubMed: 35652133
DOI: 10.1002/jmv.27902 -
Journal of Virology Jun 2022Poxvirus proteins remodel signaling throughout the cell by targeting host enzymes for inhibition and redirection. Recently, it was discovered that early in infection the...
Poxvirus proteins remodel signaling throughout the cell by targeting host enzymes for inhibition and redirection. Recently, it was discovered that early in infection the vaccinia virus (VACV) B12 pseudokinase copurifies with the cellular kinase VRK1, a proviral factor, in the nucleus. Although the formation of this complex correlates with inhibition of cytoplasmic VACV DNA replication and likely has other downstream signaling consequences, the molecular mechanisms involved are poorly understood. Here, we further characterize how B12 and VRK1 regulate one another during poxvirus infection. First, we demonstrate that B12 is stabilized in the presence of VRK1 and that VRK1 and B12 coinfluence their respective solubility and subcellular localization. In this regard, we find that B12 promotes VRK1 colocalization with cellular DNA during mitosis and that B12 and VRK1 may be tethered cooperatively to chromatin. Next, we observe that the C-terminal tail of VRK1 is unnecessary for B12-VRK1 complex formation or its proviral activity. Interestingly, we identify a point mutation of B12 capable of abrogating interaction with VRK1 and which renders B12 nonrepressive during infection. Lastly, we investigated the influence of B12 on the host factor BAF and antiviral signaling pathways and find that B12 triggers redistribution of BAF from the cytoplasm to the nucleus. In addition, B12 increases DNA-induced innate immune signaling, revealing a new functional consequence of the B12 pseudokinase. Together, this study characterizes the multifaceted roles B12 plays during poxvirus infection that impact VRK1, BAF, and innate immune signaling. Protein pseudokinases comprise a considerable fraction of the human kinome, as well as other forms of life. Recent studies have demonstrated that their lack of key catalytic residues compared to their kinase counterparts does not negate their ability to intersect with molecular signal transduction. While the multifaceted roles pseudokinases can play are known, their contribution to virus infection remains understudied. Here, we further characterize the mechanism of how the VACV B12 pseudokinase and human VRK1 kinase regulate one another in the nucleus during poxvirus infection and inhibit VACV DNA replication. We find that B12 disrupts regulation of VRK1 and its downstream target BAF, while also enhancing DNA-dependent innate immune signaling. Combined with previous data, these studies contribute to the growing field of nuclear pathways targeted by poxviruses and provide evidence of unexplored roles of B12 in the activation of antiviral immunity.
Topics: DNA; Humans; Immunity, Innate; Intracellular Signaling Peptides and Proteins; Phosphorylation; Poxviridae Infections; Protein Serine-Threonine Kinases; Signal Transduction; Vaccinia; Vaccinia virus
PubMed: 35543552
DOI: 10.1128/jvi.00398-22 -
Acta Veterinaria Scandinavica Mar 2021Goatpox is a viral disease caused by infection with goatpox virus (GTPV) of the genus Capripoxvirus, Poxviridae family. Capripoxviruses cause serious disease to...
BACKGROUND
Goatpox is a viral disease caused by infection with goatpox virus (GTPV) of the genus Capripoxvirus, Poxviridae family. Capripoxviruses cause serious disease to livestock and contribute to huge economic losses. Goatpox and sheeppox are endemic to Africa, particularly north of the Equator, the Middle East and many parts of Asia. GTPV and sheeppox virus are considered host-specific; however, both strains can cause clinical disease in either goats or sheep with more severe disease in the homologous species and mild or sub-clinical infection in the other. Goatpox has never been reported in Morocco, Algeria or Tunisia despite the huge population of goats living in proximity with sheep in those countries. To evaluate the susceptibility and pathogenicity of indigenous North African goats to GTPV infection, we experimentally inoculated eight locally bred goats with a virulent Vietnamese isolate of GTPV. Two uninfected goats were kept as controls. Clinical examination was carried out daily and blood was sampled for virology and for investigating the antibody response. After necropsy, tissues were collected and assessed for viral DNA using real-time PCR.
RESULTS
Following the experimental infection, all inoculated goats displayed clinical signs characteristic of goatpox including varying degrees of hyperthermia, loss of appetite, inactivity and cutaneous lesions. The infection severely affected three of the infected animals while moderate to mild disease was noticed in the remaining goats. A high antibody response was developed. High viral DNA loads were detected in skin crusts and nodules, and subcutaneous tissue at the injection site with cycle threshold (Ct) values ranging from 14.6 to 22.9, while lower viral loads were found in liver and lung (Ct = 35.7 and 35.1). The results confirmed subcutaneous tropism of the virus.
CONCLUSION
Clinical signs of goatpox were reproduced in indigenous North African goats and confirmed a high susceptibility of the North African goat breed to GTPV infection. A clinical scoring system is proposed that can be applied in GTPV vaccine efficacy studies.
Topics: Africa, Northern; Animals; Capripoxvirus; Goat Diseases; Goats; Male; Poxviridae Infections
PubMed: 33663573
DOI: 10.1186/s13028-021-00574-2 -
Journal of Veterinary Diagnostic... May 2018A group of Holstein first-calved heifers developed small pustules and ulcers on the vulva and in the vagina during the first 1-4 wk postpartum. The lesions varied from...
A group of Holstein first-calved heifers developed small pustules and ulcers on the vulva and in the vagina during the first 1-4 wk postpartum. The lesions varied from small red pinpoint foci to pustules and ulcers, 3-5 mm diameter. Some ulcers coalesced to form large ulcerated areas up to 15 mm diameter. In some animals, these ulcers progressed to become deep ulceration of the vaginal and vulvar mucosa with >50% of the mucosa involved. Vaginal biopsies from 4 heifers and vaginal individual swabs from 8 heifers for a combined sampling of 9 heifers were taken for clinical assessment. Six of the 9 heifers had parapoxvirus based on histopathology and/or PCR. Histologic examination of the biopsies of the pustules identified ballooning degeneration of the epithelium with degenerate epithelium containing eosinophilic intracytoplasmic inclusions consistent with a parapoxvirus in 3 of 4 biopsies. Testing for bovine herpesvirus 1, 2, and 4, bovine viral diarrhea virus, bovine papular stomatitis virus, and orf virus remained negative.
Topics: Animals; Animals, Newborn; California; Cattle; Cattle Diseases; Dairying; Disease Outbreaks; Female; Parapoxvirus; Polymerase Chain Reaction; Poxviridae Infections; Vulvovaginitis
PubMed: 29429402
DOI: 10.1177/1040638718758829 -
Animal Health Research Reviews Jun 2021Contagious ecthyma (CE) is an infectious disease of small ruminants caused by a parapoxvirus of family Poxviridae subfamily Chordopoxvirinae. The disease is obviously...
Contagious ecthyma (CE) is an infectious disease of small ruminants caused by a parapoxvirus of family Poxviridae subfamily Chordopoxvirinae. The disease is obviously distinguished by an establishment of scabby lesions and ulcerative formation on less hairy areas including muzzle, ears, nostril, and sometimes on genitalia. The disease is endemic in sheep and goats. The virus is transmissible to other ruminants and is a public health concern in humans. Although the disease is known as self-limiting, it may cause a significant economic threat and financial losses due to lower productivity in livestock production. Information with regard to the risk of the disease and epidemiology in most parts of the world is underreported. This paper aims to provide relevant information about the epidemiology of CE in selected regions of Europe, South America, North America, Asia, Africa, and Australia. An in-depth comprehension of virus infection, diagnoses, and management of the disease will enable farmers, researchers, veterinarians, abattoir workers, health personnel, and border controllers to improve their measures, skills, and effectiveness toward disease prevention and control, toward reducing unnecessary economic loss among farmers. A herd health program for significant improvement in management and productivity of livestock demands a well planned extension program that ought to encourage farmers to equip themselves with adequate skills for animal healthcare.
Topics: Animals; Ecthyma, Contagious; Goat Diseases; Goats; Humans; Orf virus; Ruminants; Sheep; Sheep Diseases
PubMed: 34016216
DOI: 10.1017/S1466252320000018 -
Acta Tropica Jun 2016Camelpox caused by a Camelpox virus (CMLV) is a very important host specific viral disease of camel. It is highly contagious in nature and causes serious impact on... (Review)
Review
Camelpox caused by a Camelpox virus (CMLV) is a very important host specific viral disease of camel. It is highly contagious in nature and causes serious impact on health even mortality of camels and economic losses to the camel owners. It manifests itself either in the local/mild or generalized/severe form. Various outbreaks of different pathogenicity have been reported from camel dwelling areas of the world. CMLV has been characterized in embryonated chicken eggs with the production of characteristic pock lesions and in various cell lines with the capacity to induce giant cells. Being of Poxviridae family, CMLV employs various strategies to impede host immune system and facilitates its own pathogenesis. Both live and attenuated vaccine has been found effective against CMLV infection. The present review gives a comprehensive overview of camelpox disease with respect to its transmission, epidemiology, virion characteristics, viral life cycle, host interaction and its immune modulation.
Topics: Animals; Camelus; Disease Outbreaks; Orthopoxvirus; Poxviridae Infections
PubMed: 26902797
DOI: 10.1016/j.actatropica.2016.02.014 -
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 -
Journal of Virology May 2018Cytosolic recognition of DNA has emerged as a critical cellular mechanism of host immune activation upon pathogen invasion. The central cytosolic DNA sensor cGAS...
Cytosolic recognition of DNA has emerged as a critical cellular mechanism of host immune activation upon pathogen invasion. The central cytosolic DNA sensor cGAS activates STING, which is phosphorylated, dimerizes and translocates from the endoplasmic reticulum (ER) to a perinuclear region to mediate IRF-3 activation. Poxviruses are double-stranded DNA viruses replicating in the cytosol and hence likely to trigger cytosolic DNA sensing. Here, we investigated the activation of innate immune signaling by 4 different strains of the prototypic poxvirus vaccinia virus (VACV) in a cell line proficient in DNA sensing. Infection with the attenuated VACV strain MVA activated IRF-3 via cGAS and STING, and accordingly STING dimerized and was phosphorylated during MVA infection. Conversely, VACV strains Copenhagen and Western Reserve inhibited STING dimerization and phosphorylation during infection and in response to transfected DNA and cyclic GMP-AMP, thus efficiently suppressing DNA sensing and IRF-3 activation. A VACV deletion mutant lacking protein C16, thought to be the only viral DNA sensing inhibitor acting upstream of STING, retained the ability to block STING activation. Similar inhibition of DNA-induced STING activation was also observed for cowpox and ectromelia viruses. Our data demonstrate that virulent poxviruses possess mechanisms for targeting DNA sensing at the level of the cGAS-STING axis and that these mechanisms do not operate in replication-defective strains such as MVA. These findings shed light on the role of cellular DNA sensing in poxvirus-host interactions and will open new avenues to determine its impact on VACV immunogenicity and virulence. Poxviruses are double-stranded DNA viruses infecting a wide range of vertebrates and include the causative agent of smallpox (variola virus) and its vaccine vaccinia virus (VACV). Despite smallpox eradication VACV remains of interest as a therapeutic. Attenuated strains are popular vaccine candidates, whereas replication-competent strains are emerging as efficient oncolytics in virotherapy. The successful therapeutic use of VACV depends on a detailed understanding of its ability to modulate host innate immune responses. DNA sensing is a critical cellular mechanism for pathogen detection and activation of innate immunity that is centrally coordinated by the endoplasmic reticulum-resident protein STING. Here, STING is shown to mediate immune activation in response to MVA, but not in response to virulent VACV strains or other virulent poxviruses, which prevent STING activation and DNA sensing during infection and after DNA transfection. These results provide new insights into poxvirus immune evasion and have implications in the rational design of VACV-based therapeutics.
Topics: Cell Line; Cytosol; HEK293 Cells; Humans; Membrane Proteins; Phosphorylation; Poxviridae; Poxviridae Infections; Protein Multimerization; THP-1 Cells; Virulence; Virus Replication
PubMed: 29491158
DOI: 10.1128/JVI.02145-17 -
Anais Brasileiros de Dermatologia 2015Milker's nodule is an occupational viral skin disease of universal distribution, caused by the Paravaccinia virus and that occurs in individuals who deal with dairy...
Milker's nodule is an occupational viral skin disease of universal distribution, caused by the Paravaccinia virus and that occurs in individuals who deal with dairy cattle herds. We describe a case acquired due to lack of use of PPE (Personal Protective Equipment) and perform a literature review.
Topics: Animals; Biopsy; Cattle; Disease Progression; Female; Hand Dermatoses; Humans; Middle Aged; Occupational Diseases; Poxviridae Infections; Pseudocowpox Virus; Skin Diseases, Viral
PubMed: 26131876
DOI: 10.1590/abd1806-4841.20153283 -
Anais Brasileiros de Dermatologia 2022Monkeypox is an emerging infection that has spread to all continents since May 2022. It is caused by the zoonotic monkeypox virus, consisting of double-stranded DNA,...
Monkeypox is an emerging infection that has spread to all continents since May 2022. It is caused by the zoonotic monkeypox virus, consisting of double-stranded DNA, belonging to the Orthopoxvirus genus of the Poxviridae family, which has high transmissibility, especially by contact with the skin, favoring its sexual transmission. This case report describes a same-sex male couple, both aged 28 years old, without comorbidities. In the index case, perioral and penile lesions started ten days before the consultation, with rapid progression and a high fever that started eight days after the appearance of the lesions. In the second case, the perioral lesions started three days after the partner; however, he remained afebrile. Both were isolated, treated with symptomatic measures, and, after ulceration, the lesions completely regressed in 14 days. Dermatologists should be aware of manifestations of monkeypox, which may include vesiculopustular lesions in areas of sexual contact, as well as oligosymptomatic cases or cases with few skin lesions.
Topics: Adult; Humans; Male; Mpox (monkeypox); Monkeypox virus; Skin
PubMed: 36137892
DOI: 10.1016/j.abd.2022.08.002