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PLoS Pathogens Mar 2021
Review
Topics: Animals; Chiroptera; Drosophila Proteins; Humans; Nucleotides, Cyclic; Poxviridae; Poxviridae Infections; RNA; Transcription Factors
PubMed: 33735254
DOI: 10.1371/journal.ppat.1009372 -
Viruses Mar 2023Mpox, formerly called monkeypox, is now the most serious orthopoxvirus (OPXV) infection in humans. This zoonotic disease has been gradually re-emerging in humans with an... (Review)
Review
Mpox, formerly called monkeypox, is now the most serious orthopoxvirus (OPXV) infection in humans. This zoonotic disease has been gradually re-emerging in humans with an increasing frequency of cases found in endemic areas, as well as an escalating frequency and size of epidemics outside of endemic areas in Africa. Currently, the largest known mpox epidemic is spreading throughout the world, with over 85,650 cases to date, mostly in Europe and North America. These increased endemic cases and epidemics are likely driven primarily by decreasing global immunity to OPXVs, along with other possible causes. The current unprecedented global outbreak of mpox has demonstrated higher numbers of human cases and greater human-to-human transmission than previously documented, necessitating an urgent need to better understand this disease in humans and animals. Monkeypox virus (MPXV) infections in animals, both naturally occurring and experimental, have provided critical information about the routes of transmission; the viral pathogenicity factors; the methods of control, such as vaccination and antivirals; the disease ecology in reservoir host species; and the conservation impacts on wildlife species. This review briefly described the epidemiology and transmission of MPXV between animals and humans and summarizes past studies on the ecology of MPXV in wild animals and experimental studies in captive animal models, with a focus on how animal infections have informed knowledge concerning various aspects of this pathogen. Knowledge gaps were highlighted in areas where future research, both in captive and free-ranging animals, could inform efforts to understand and control this disease in both humans and animals.
Topics: Animals; Humans; Monkeypox virus; Animals, Wild; Mpox (monkeypox); Zoonoses; Poxviridae Infections; Models, Animal
PubMed: 37112885
DOI: 10.3390/v15040905 -
Viruses Dec 2020Akhmeta virus is a zoonotic first identified in 2013 in the country of Georgia. Subsequent ecological investigations in Georgia have found evidence that this virus is...
Akhmeta virus is a zoonotic first identified in 2013 in the country of Georgia. Subsequent ecological investigations in Georgia have found evidence that this virus is widespread in its geographic distribution within the country and in its host-range, with rodents likely involved in its circulation in the wild. Yet, little is known about the pathogenicity of this virus in rodents. We conducted the first laboratory infection of Akhmeta virus in CAST/EiJ to further characterize this novel virus. We found a dose-dependent effect on mortality and weight loss ( < 0.05). Anti-orthopoxvirus antibodies were detected in the second- and third-highest dose groups (5 × 10 pfu and 3 × 10 pfu) at euthanasia by day 10, and day 14 post-infection, respectively. Anti-orthopoxvirus antibodies were not detected in the highest dose group (3 × 10 pfu), which were euthanized at day 7 post-infection and had high viral load in tissues, suggesting they succumbed to disease prior to mounting an effective immune response. In order of highest burden, viable virus was detected in the nostril, lung, tail, liver and spleen. All individuals tested in the highest dose groups were DNAemic. Akhmeta virus was highly pathogenic in CAST/EiJ causing 100% mortality when ≥3 × 10 pfu was administered.
Topics: Animal Diseases; Animals; Female; Laboratory Infection; Mice; Orthopoxvirus; Poxviridae Infections; Serologic Tests; Viral Load
PubMed: 33317132
DOI: 10.3390/v12121416 -
Journal of Virology Mar 2023Recent studies have begun to reveal the complex and multifunctional roles of -methyladenosine (mA) modifications and their associated writer, reader, and eraser proteins...
Recent studies have begun to reveal the complex and multifunctional roles of -methyladenosine (mA) modifications and their associated writer, reader, and eraser proteins in infection by diverse RNA and DNA viruses. However, little is known about their regulation and functions during infection by several viruses, including poxviruses. Here, we show that members of the YTH Domain Family (YTHDF), in particular YTHDF2, are downregulated as the prototypical poxvirus, vaccinia virus (VacV) enters later stages of replication in a variety of natural target cell types, but not in commonly used transformed cell lines wherein the control of YTHDF2 expression appears to be dysregulated. YTHDF proteins also decreased at late stages of infection by herpes simplex virus 1 (HSV-1) but not human cytomegalovirus, suggesting that YTHDF2 is downregulated in response to infections that induce host shutoff. In line with this idea, YTHDF2 was potently downregulated upon infection with a VacV mutant expressing catalytically inactive forms of the decapping enzymes, D9 and D10, which fails to degrade dsRNA and induces a protein kinase R response that itself inhibits protein synthesis. Overexpression and RNAi-mediated depletion approaches further demonstrate that YTHDF2 does not directly affect VacV replication. Instead, experimental downregulation of YTHDF2 or the related family member, YTHDF1, induces a potent increase in interferon-stimulated gene expression and establishes an antiviral state that suppresses infection by either VacV or HSV-1. Combined, our data suggest that YTHDF2 is destabilized in response to infection-induced host shutoff and serves to augment host antiviral responses. There is increasing recognition of the importance of -methyladenosine (mA) modifications to both viral and host mRNAs and the complex roles this modification plays in determining the fate of infection by diverse RNA and DNA viruses. However, in many instances, the functional contributions and importance of specific mA writer, reader, and eraser proteins remains unknown. Here, we show that natural target cells but not transformed cell lines downregulate the YTH Domain Family (YTHDF) of mA reader proteins, in particular YTHDF2, in response to shutoff of protein synthesis upon infection with the large DNA viruses, vaccinia virus (VacV), or herpes simplex virus type 1. We further reveal that YTHDF2 downregulation also occurs as part of the host protein kinase R response to a VacV shutoff mutant and that this downregulation of YTHDF family members functions to enhance interferon-stimulated gene expression to create an antiviral state.
Topics: Humans; Gene Expression; Interferons; Poxviridae; Protein Kinases; RNA-Binding Proteins; Transcription Factors; Vaccinia; Vaccinia virus; Virus Replication; Poxviridae Infections; Host-Pathogen Interactions
PubMed: 36916936
DOI: 10.1128/jvi.01758-22 -
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 -
Journal of Virology May 2013Poxvirus infections have been found in 230 species of wild and domestic birds worldwide in both terrestrial and marine environments. This ubiquity raises the question of...
Poxvirus infections have been found in 230 species of wild and domestic birds worldwide in both terrestrial and marine environments. This ubiquity raises the question of how infection has been transmitted and globally dispersed. We present a comprehensive global phylogeny of 111 novel poxvirus isolates in addition to all available sequences from GenBank. Phylogenetic analysis of the Avipoxvirus genus has traditionally relied on one gene region (4b core protein). In this study we expanded the analyses to include a second locus (DNA polymerase gene), allowing for a more robust phylogenetic framework, finer genetic resolution within specific groups, and the detection of potential recombination. Our phylogenetic results reveal several major features of avipoxvirus evolution and ecology and propose an updated avipoxvirus taxonomy, including three novel subclades. The characterization of poxviruses from 57 species of birds in this study extends the current knowledge of their host range and provides the first evidence of the phylogenetic effect of genetic recombination of avipoxviruses. The repeated occurrence of avian family or order-specific grouping within certain clades (e.g., starling poxvirus, falcon poxvirus, raptor poxvirus, etc.) indicates a marked role of host adaptation, while the sharing of poxvirus species within prey-predator systems emphasizes the capacity for cross-species infection and limited host adaptation. Our study provides a broad and comprehensive phylogenetic analysis of the Avipoxvirus genus, an ecologically and environmentally important viral group, to formulate a genome sequencing strategy that will clarify avipoxvirus taxonomy.
Topics: Animals; Avipoxvirus; Bird Diseases; Birds; Host Specificity; Molecular Sequence Data; Phylogeny; Poxviridae Infections; Recombination, Genetic
PubMed: 23408635
DOI: 10.1128/JVI.03183-12 -
Wilderness & Environmental Medicine Dec 2021Zoonotic orthopoxvirus outbreaks have occurred repeatedly worldwide, including monkeypox in Africa and the United States, cowpox in Europe, camelpox in the Middle East... (Review)
Review
Zoonotic orthopoxvirus outbreaks have occurred repeatedly worldwide, including monkeypox in Africa and the United States, cowpox in Europe, camelpox in the Middle East and India, buffalopox in India, vaccinia in South America, and novel emerging orthopoxvirus infections in the United States, Europe, Asia, and South America. Waning smallpox immunity may increase the potential for animal-to-human transmission followed by further community transmission person-to-person (as demonstrated by monkeypox and buffalopox outbreaks) and by contact with fomites (as demonstrated by camelpox, cowpox, and, possibly, Alaskapox). The objectives of this review are to describe the disease ecology, epidemiology, clinical manifestations, prevention, and control of human infections with animal orthopoxviruses and to discuss the association with diminished population herd immunity formerly induced by vaccinia vaccination against smallpox. Internet search engines were queried with key words, and case reports, case series, seroprevalence studies, and epidemiologic investigations were found for review.
Topics: Animals; Humans; Orthopoxvirus; Poxviridae Infections; Seroepidemiologic Studies; United States; Vaccinia virus; Variola virus
PubMed: 34563454
DOI: 10.1016/j.wem.2021.08.003 -
Clinical Infectious Diseases : An... Jun 2017Human infection by orthopoxviruses is being reported with increasing frequency, attributed in part to the cessation of smallpox vaccination and concomitant waning of...
BACKGROUND.
Human infection by orthopoxviruses is being reported with increasing frequency, attributed in part to the cessation of smallpox vaccination and concomitant waning of population-level immunity. In July 2015, a female resident of interior Alaska presented to an urgent care clinic with a dermal lesion consistent with poxvirus infection. Laboratory testing of a virus isolated from the lesion confirmed infection by an Orthopoxvirus.
METHODS.
The virus isolate was characterized by using electron microscopy and nucleic acid sequencing. An epidemiologic investigation that included patient interviews, contact tracing, and serum testing, as well as environmental and small-mammal sampling, was conducted to identify the infection source and possible additional cases.
RESULTS.
Neither signs of active infection nor evidence of recent prior infection were observed in any of the 4 patient contacts identified. The patient's infection source was not definitively identified. Potential routes of exposure included imported fomites from Azerbaijan via the patient's cohabiting partner or wild small mammals in or around the patient's residence. Phylogenetic analyses demonstrated that the virus represents a distinct and previously undescribed genetic lineage of Orthopoxvirus, which is most closely related to the Old World orthopoxviruses.
CONCLUSIONS.
Investigation findings point to infection of the patient after exposure in or near Fairbanks. This conclusion raises questions about the geographic origins (Old World vs North American) of the genus Orthopoxvirus. Clinicians should remain vigilant for signs of poxvirus infection and alert public health officials when cases are suspected.
Topics: Alaska; Animals; Antibodies, Viral; DNA, Viral; Female; Fomites; Humans; Mammals; Microscopy, Electron; Middle Aged; Orthopoxvirus; Phylogeny; Poxviridae Infections; Sequence Analysis, DNA; Skin
PubMed: 28329402
DOI: 10.1093/cid/cix219 -
Proceedings of the National Academy of... Oct 1996Vaccinia virus, no longer required for immunization against smallpox, now serves as a unique vector for expressing genes within the cytoplasm of mammalian cells. As a... (Review)
Review
Vaccinia virus, no longer required for immunization against smallpox, now serves as a unique vector for expressing genes within the cytoplasm of mammalian cells. As a research tool, recombinant vaccinia viruses are used to synthesize and analyze the structure-function relationships of proteins, determine the targets of humoral and cell-mediated immunity, and investigate the types of immune response needed for protection against specific infectious diseases and cancer. The vaccine potential of recombinant vaccinia virus has been realized in the form of an effective oral wild-life rabies vaccine, although no product for humans has been licensed. A genetically altered vaccinia virus that is unable to replicate in mammalian cells and produces diminished cytopathic effects retains the capacity for high-level gene expression and immunogenicity while promising exceptional safety for laboratory workers and potential vaccine recipients.
Topics: AIDS Vaccines; Acquired Immunodeficiency Syndrome; Animals; Antibody Formation; Cells, Cultured; Genetic Engineering; Genetic Vectors; Humans; Immunity, Cellular; Mammals; Poxviridae; Poxviridae Infections; Safety; Smallpox; Transfection; Vaccination; Vaccines, Synthetic; Vaccinia virus; Viral Proteins
PubMed: 8876137
DOI: 10.1073/pnas.93.21.11341 -
Clinical Microbiology Reviews Apr 2001Poxviruses continue to pose a major threat to human health. Monkeypox is endemic in central Africa, and the discontinuation of the vaccination (with vaccinia virus) has... (Review)
Review
Poxviruses continue to pose a major threat to human health. Monkeypox is endemic in central Africa, and the discontinuation of the vaccination (with vaccinia virus) has rendered most humans vulnerable to variola virus, the etiologic agent of smallpox, should this virus be used in biological warfare or terrorism. However, a large variety of compounds have been described that are potent inhibitors of vaccinia virus replication and could be expected to be active against other poxviruses as well. These compounds could be grouped in different classes: (i) IMP dehydrogenase inhibitors (e.g., EICAR); (ii) SAH hydrolase inhibitors (e.g., 5'-noraristeromycin, 3-deazaneplanocin A, and various neplanocin A derivatives); (iii) OMP decarboxylase inhibitors (e.g., pyrazofurin) and CTP synthetase inhibitors (e.g., cyclopentenyl cytosine); (iv) thymidylate synthase inhibitors (e.g., 5-substituted 2'-deoxyuridines); (v) nucleoside analogues that are targeted at viral DNA synthesis (e.g., Ara-A); (vi) acyclic nucleoside phosphonates [e.g., (S)-HPMPA and (S)-HPMPC (cidofovir)]; and (vii) polyanionic substances (e.g., polyacrylic acid). All these compounds could be considered potential candidate drugs for the therapy and prophylaxis of poxvirus infections at large. Some of these compounds, in particular polyacrylic acid and cidofovir, were found to generate, on single-dose administration, a long-lasting protective efficacy against vaccinia virus infection in vivo. Cidofovir, which has been approved for the treatment of cytomegalovirus retinitis in immunocompromised patients, was also found to protect mice, again when given as a single dose, against a lethal aerosolized or intranasal cowpox virus challenge. In a biological warfare scenario, it would be advantageous to be able to use a single treatment for an individual exposed to an aerosolized poxvirus. Cidofovir thus holds great promise for treating human smallpox, monkeypox, and other poxvirus infections. Anecdotal experience points to the efficacy of cidofovir in the treatment of the poxvirus infections molluscum contagiosum and orf (ecthyma contagiosum) in immunosuppressed patients.
Topics: Antiviral Agents; Humans; Nucleosides; Poxviridae; Poxviridae Infections; Vaccinia virus
PubMed: 11292644
DOI: 10.1128/CMR.14.2.382-397.2001