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Viruses Dec 2020The global emergence of zoonotic viruses, including poxviruses, poses one of the greatest threats to human and animal health. Forty years after the eradication of... (Review)
Review
The global emergence of zoonotic viruses, including poxviruses, poses one of the greatest threats to human and animal health. Forty years after the eradication of smallpox, emerging zoonotic orthopoxviruses, such as monkeypox, cowpox, and vaccinia viruses continue to infect humans as well as wild and domestic animals. Currently, the geographical distribution of poxviruses in a broad range of hosts worldwide raises concerns regarding the possibility of outbreaks or viral dissemination to new geographical regions. Here, we review the global host ranges and current epidemiological understanding of zoonotic orthopoxviruses while focusing on orthopoxviruses with epidemic potential, including monkeypox, cowpox, and vaccinia viruses.
Topics: Animals; Geography, Medical; Host Specificity; Humans; Orthopoxvirus; Poxviridae Infections; Viral Zoonoses
PubMed: 33396609
DOI: 10.3390/v13010043 -
PLoS Pathogens Oct 2021Viruses have evolved mechanisms to subvert critical cellular signaling pathways that regulate a wide range of cellular functions, including cell differentiation,...
Viruses have evolved mechanisms to subvert critical cellular signaling pathways that regulate a wide range of cellular functions, including cell differentiation, proliferation and chemotaxis, and innate immune responses. Here, we describe a novel ORFV protein, ORFV113, that interacts with the G protein-coupled receptor Lysophosphatidic acid receptor 1 (LPA1). Consistent with its interaction with LPA1, ORFV113 enhances p38 kinase phosphorylation in ORFV infected cells in vitro and in vivo, and in cells transiently expressing ORFV113 or treated with soluble ORFV113. Infection of cells with virus lacking ORFV113 (OV-IA82Δ113) significantly decreased p38 phosphorylation and viral plaque size. Infection of cells with ORFV in the presence of a p38 kinase inhibitor markedly diminished ORFV replication, highlighting importance of p38 signaling during ORFV infection. ORFV113 enhancement of p38 activation was prevented in cells in which LPA1 expression was knocked down and in cells treated with LPA1 inhibitor. Infection of sheep with OV-IA82Δ113 led to a strikingly attenuated disease phenotype, indicating that ORFV113 is a major virulence determinant in the natural host. Notably, ORFV113 represents the first viral protein that modulates p38 signaling via interaction with LPA1 receptor.
Topics: Animals; MAP Kinase Signaling System; Parapoxvirus; Poxviridae Infections; Receptors, Lysophosphatidic Acid; Sheep; Viral Proteins
PubMed: 34614034
DOI: 10.1371/journal.ppat.1009971 -
Antiviral Research Jul 2002Cidofovir [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine, HPMPC] has since 1996 been licensed for clinical use in the treatment of cytomegalovirus (CMV) retinitis... (Comparative Study)
Comparative Study Review
Cidofovir [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine, HPMPC] has since 1996 been licensed for clinical use in the treatment of cytomegalovirus (CMV) retinitis in AIDS patients. Cidofovir has broad-spectrum activity against virtually all DNA viruses, including herpes-, adeno-, polyoma-, papilloma- and poxviruses. Among the poxviruses, vaccinia, variola (smallpox), cowpox, monkeypox, camelpox, molluscum contagiosum and orf have proven sensitive to the inhibitory effects of cidofovir. In vivo, cidofovir has shown high efficacy, even after administration of a single systemic (intraperitoneal) or intranasal (aerosolized) dose, in protecting mice from a lethal respiratory infection with either vaccinia or cowpox. Cidofovir has also demonstrated high effectiveness in the treatment of vaccinia virus infection in severe combined immune deficiency mice. In humans, cidofovir has been used successfully in the treatment, by both the topical and intravenous route, of recalcitrant molluscum contagiosum and orf in immunocompromised patients. Taken together, these data indicate that cidofovir should be effective in the therapy and short-term prophylaxis of smallpox and related poxvirus infections in humans, as well as the treatment of the complications of vaccinia that may arise in immunocompromised patients inadvertently inoculated with the smallpox vaccine (vaccinia).
Topics: Administration, Intranasal; Animals; Antiviral Agents; Cidofovir; Cytosine; DNA, Viral; Disease Models, Animal; Humans; Immunocompromised Host; Injections, Intraperitoneal; Injections, Intravenous; Organophosphonates; Organophosphorus Compounds; Poxviridae; Poxviridae Infections
PubMed: 12076747
DOI: 10.1016/s0166-3542(02)00008-6 -
Philosophical Transactions of the Royal... May 2018Provision of supplementary food for wild birds at garden feeding stations is a common, large-scale and year-round practice in multiple countries including Great Britain... (Review)
Review
Provision of supplementary food for wild birds at garden feeding stations is a common, large-scale and year-round practice in multiple countries including Great Britain (GB). While these additional dietary resources can benefit wildlife, there is a concomitant risk of disease transmission, particularly when birds repeatedly congregate in the same place at high densities and through interactions of species that would not normally associate in close proximity. Citizen science schemes recording garden birds are popular and can integrate disease surveillance with population monitoring, offering a unique opportunity to explore inter-relationships between supplementary feeding, disease epidemiology and population dynamics. Here, we present findings from a national surveillance programme in GB and note the dynamism of endemic and emerging diseases over a 25-year period, focusing on protozoal (finch trichomonosis), viral (Paridae pox) and bacterial (passerine salmonellosis) diseases with contrasting modes of transmission. We also examine the occurrence of mycotoxin contamination of food residues in bird feeders, which present both a direct and indirect (though immunosuppression) risk to wild bird health. Our results inform evidence-based mitigation strategies to minimize anthropogenically mediated health hazards, while maintaining the benefits of providing supplementary food for wild birds.This article is part of the theme issue 'Anthropogenic resource subsidies and host-parasite dynamics in wildlife'.
Topics: Animal Feed; Animals; Bird Diseases; Epidemiological Monitoring; Humans; Immunity, Innate; Mycotoxins; Passeriformes; Population Dynamics; Poxviridae Infections; Risk Factors; Salmonella Infections; Trichomonas Infections; United Kingdom
PubMed: 29531146
DOI: 10.1098/rstb.2017.0091 -
Cells Dec 2023Conventional dendritic cells (cDCs) are innate immune cells that play a pivotal role in inducing antiviral adaptive immune responses due to their extraordinary ability...
Conventional dendritic cells (cDCs) are innate immune cells that play a pivotal role in inducing antiviral adaptive immune responses due to their extraordinary ability to prime and polarize naïve T cells into different effector T helper (Th) subsets. The two major subpopulations of cDCs, cDC1 (CD8α in mice and CD141 in human) and cDC2 (CD11b in mice and CD1c in human), can preferentially polarize T cells toward a Th1 and Th2 phenotype, respectively. During infection with ectromelia virus (ECTV), an orthopoxvirus from the family, the timing and activation of an appropriate Th immune response contributes to the resistance (Th1) or susceptibility (Th2) of inbred mouse strains to the lethal form of mousepox. Due to the high plasticity and diverse properties of cDC subpopulations in regulating the quality of a specific immune response, in the present study we compared the ability of splenic cDC1 and cDC2 originating from different ECTV-infected mouse strains to mature, activate, and polarize the Th immune response during mousepox. Our results demonstrated that during early stages of mousepox, both cDC subsets from resistant C57BL/6 and susceptible BALB/c mice were activated upon in vivo ECTV infection. These cells exhibited elevated levels of surface MHC class I and II, and co-stimulatory molecules and showed enhanced potential to produce cytokines. However, both cDC subsets from BALB/c mice displayed a higher maturation status than that of their counterparts from C57BL/6 mice. Despite their higher activation status, cDC1 and cDC2 from susceptible mice produced low amounts of Th1-polarizing cytokines, including IL-12 and IFN-γ, and the ability of these cells to stimulate the proliferation and Th1 polarization of allogeneic CD4 T cells was severely compromised. In contrast, both cDC subsets from resistant mice produced significant amounts of Th1-polarizing cytokines and demonstrated greater capability in differentiating allogeneic T cells into Th1 cells compared to cDCs from BALB/c mice. Collectively, our results indicate that in the early stages of mousepox, splenic cDC subpopulations from the resistant mouse strain can better elicit a Th1 cell-mediated response than the susceptible strain can, probably contributing to the induction of the protective immune responses necessary for the control of virus dissemination and for survival from ECTV challenge.
Topics: Humans; Animals; Mice; Mice, Inbred C57BL; Ectromelia, Infectious; Poxviridae Infections; Cytokines; Dendritic Cells
PubMed: 38201217
DOI: 10.3390/cells13010013 -
British Medical Journal Feb 1977
Topics: Africa; Animals; Child; Haplorhini; Humans; Monkey Diseases; Monkeypox virus; Poxviridae Infections; Smallpox
PubMed: 191140
DOI: No ID Found -
Expert Review of Vaccines Aug 2011Less than 200 years after its introduction, widespread use of vaccinia virus (VACV) as a smallpox vaccine has eradicated variola virus. Along with the remarkable success... (Review)
Review
Less than 200 years after its introduction, widespread use of vaccinia virus (VACV) as a smallpox vaccine has eradicated variola virus. Along with the remarkable success of the vaccination program, frequent and sometimes severe adverse reactions to VACV were encountered. After eradication, VACV has been reserved for select populations who might be at significant risk for orthopoxvirus infections. Events over the past decade have renewed concerns over the potential use of variola virus as a biological weapon. Accordingly, interest in VACV and attenuated derivatives has increased, both as vaccines against smallpox and as vectors for other vaccines. This article will focus on new developments in the field of orthopoxvirus immunization and will highlight recent advances in the use of vaccinia viruses as vectors for infectious diseases and malignancies.
Topics: Animals; Cancer Vaccines; Genetic Vectors; Humans; Neoplasms; Poxviridae Infections; Smallpox Vaccine; Vaccinia virus
PubMed: 21854314
DOI: 10.1586/erv.11.79 -
Antiviral Research Jan 2003Several animal models using mice (most frequently), rabbits, or monkeys have been used to identify compounds active against orthopoxvirus infections. The treatment of... (Review)
Review
Several animal models using mice (most frequently), rabbits, or monkeys have been used to identify compounds active against orthopoxvirus infections. The treatment of vaccinia virus infections has been well studied in models involving infection of scarified skin or eyes, or resulting from intravenous, intraperitoneal, intracerebral, or intranasal virus inoculation. Cowpox virus has been used in intranasal or aerosol infection studies to evaluate the treatment of lethal respiratory infections. Rabbitpox, monkeypox, and variola viruses have been employed to a lesser extent than the other viruses in chemotherapy experiments. A review of the literature over the past 50 years has identified a number of compounds effective in treating one or more of these infections, which include thiosemicarbazones, nucleoside and nucleotide analogs, interferon, interferon inducers, and other unrelated compounds. Substances that appear to have the greatest potential as anti-orthopoxvirus agents are the acyclic nucleotides, (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (cidofovir, HPMPC) and 1-[((S)-2-hydroxy-2-oxo-1,4,2-dioxaphosphorinan-5-yl)methyl]cytosine (cyclic HPMPC), and the acyclic nucleoside analog, 2-amino-7-[(1,3-dihydroxy-2-propoxy)methyl]purine (S2242). Other classes of compounds that have not been sufficiently studied in lethal infection models and deserve further consideration are thiosemicarbazones related to methisazone, and analogs of adenosine-N(1)-oxide and 1-(benzyloxy)adenosine.
Topics: Animals; Antiviral Agents; Bioterrorism; Cidofovir; Cytosine; Disease Models, Animal; Humans; Mice; Mice, SCID; Nucleosides; Organophosphonates; Organophosphorus Compounds; Orthopoxvirus; Poxviridae Infections; Rabbits; Smallpox; Thiosemicarbazones
PubMed: 12615302
DOI: 10.1016/s0166-3542(02)00199-7 -
Trends in Pharmacological Sciences Oct 2002Although it is often stated that only vaccination would be able to contain or protect the population against a catastrophic smallpox outbreak, the acyclic nucleoside... (Review)
Review
Although it is often stated that only vaccination would be able to contain or protect the population against a catastrophic smallpox outbreak, the acyclic nucleoside phosphonate analog cidofovir offers a valuable alternative for the therapy and short-term pre- and post-exposure prophylaxis, not only of smallpox but also of other poxvirus infections and DNA viruses. Cidofovir has proven effective against vaccinia, cowpox and monkeypox in various animal model infections. In cell culture, cidofovir has demonstrated activity against variola virus, the etiological agent of smallpox, and in patients it has shown marked efficacy against molluscum contagiosum and orf, two poxvirus infections. Cidofovir is available as an aqueous solution for intravenous administration and could be reformulated for topical (cream or gel), intranasal (aerosol) or peroral (as a lipid prodrug) use, should the need arise.
Topics: Antiviral Agents; Cidofovir; Cytosine; Humans; Organophosphonates; Organophosphorus Compounds; Poxviridae Infections; Prodrugs
PubMed: 12368068
DOI: 10.1016/s0165-6147(02)02091-6 -
Viruses Aug 2017Taterapox virus (TATV), which was isolated from an African gerbil () in 1975, is the most closely related virus to variola; however, only the original report has...
Taterapox virus (TATV), which was isolated from an African gerbil () in 1975, is the most closely related virus to variola; however, only the original report has examined its virology. We have evaluated the tropism of TATV in vivo in small animals. We found that TATV does not infect , a species of African dormouse, but does induce seroconversion in the Mongolian gerbil () and in mice; however, in wild-type mice and gerbils, the virus produces an unapparent infection. Following intranasal and footpad inoculations with 1 × 10⁶ plaque forming units (PFU) of TATV, immunocompromised mice showed signs of disease but did not die; however, SCID mice were susceptible to intranasal and footpad infections with 100% mortality observed by Day 35 and Day 54, respectively. We show that death is unlikely to be a result of the virus mutating to have increased virulence and that SCID mice are capable of transmitting TATV to C57BL/6 and C57BL/6 animals; however, transmission did not occur from TATV inoculated wild-type or mice. Comparisons with ectromelia (the etiological agent of mousepox) suggest that TATV behaves differently both at the site of inoculation and in the immune response that it triggers.
Topics: Animals; Antiviral Agents; Disease Models, Animal; Ectromelia virus; Ectromelia, Infectious; Host Specificity; Mice; Mice, Inbred C57BL; Mice, SCID; Orthopoxvirus; Poxviridae Infections; STAT1 Transcription Factor; Viral Tropism
PubMed: 28763036
DOI: 10.3390/v9080203