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PloS One Jul 2009The genus Orthopoxvirus contains several species of related viruses, including the causative agent of smallpox (Variola virus). In addition to smallpox, several other...
The genus Orthopoxvirus contains several species of related viruses, including the causative agent of smallpox (Variola virus). In addition to smallpox, several other members of the genus are capable of causing human infection, including monkeypox, cowpox, and other zoonotic rodent-borne poxviruses. Therefore, a single assay that can accurately identify all orthopoxviruses could provide a valuable tool for rapid broad orthopovirus identification. We have developed a pan-Orthopoxvirus assay for identification of all members of the genus based on four PCR reactions targeting Orthopoxvirus DNA and RNA helicase and polymerase genes. The amplicons are detected using electrospray ionization-mass spectrometry (PCR/ESI-MS) on the Ibis T5000 system. We demonstrate that the assay can detect and identify a diverse collection of orthopoxviruses, provide sub-species information and characterize viruses from the blood of rabbitpox infected rabbits. The assay is sensitive at the stochastic limit of PCR and detected virus in blood containing approximately six plaque-forming units per milliliter from a rabbitpox virus-infected rabbit.
Topics: Animals; Base Sequence; DNA Primers; DNA, Viral; Humans; Mass Spectrometry; Molecular Sequence Data; Orthopoxvirus; Polymerase Chain Reaction; Rabbits; Sequence Homology, Nucleic Acid
PubMed: 19623263
DOI: 10.1371/journal.pone.0006342 -
Antiviral Research Jan 2003The potential use of variola or another orthopoxvirus such as monkeypox as a weapon of bioterrorism has stimulated efforts to develop new drugs for treatment of smallpox... (Review)
Review
The potential use of variola or another orthopoxvirus such as monkeypox as a weapon of bioterrorism has stimulated efforts to develop new drugs for treatment of smallpox or other poxvirus infections. At the present time only cidofovir is approved for use in the emergency treatment of smallpox outbreaks. Although cidofovir is very active against the orthopoxviruses in vitro and in animal model infections, it is not active when given orally and must be administered with precaution so as to avoid renal toxicity. In an attempt to identify alternative treatment modalities for these infections we have determined the anti-poxvirus activity in vitro of most of the approved antiviral agents as well as a number of cidofovir analogs and prodrugs. From these studies, we have identified the nucleotide analog, adefovir dipivoxil, some alkoxyalkyl esters of cidofovir and a number of prodrugs of cidofovir that warrant further investigation as potential therapies for smallpox or other orthopoxvirus infections.
Topics: Adenine; Animals; Antiviral Agents; Cells, Cultured; Cidofovir; Cytosine; Humans; Mice; Microbial Sensitivity Tests; Organophosphonates; Organophosphorus Compounds; Orthopoxvirus; Virus Replication
PubMed: 12615301
DOI: 10.1016/s0166-3542(02)00198-5 -
Journal of Infection in Developing... Jun 2008The presence of zoonotic poxviruses in nature represents a potential human health risk that has to be re-evaluated by health authorities not only in developing... (Review)
Review
The presence of zoonotic poxviruses in nature represents a potential human health risk that has to be re-evaluated by health authorities not only in developing countries, but also in many developed countries. For example, buffalopox virus infection remains to be a threat to humans and cattle in India, and monkeypox virus infection persists in several inhabited places in Africa and, more recently, in the USA. There are also a great number of zoonotic transmissions of cowpox virus from cats to humans in Europe. For almost a decade in Brazil, vaccinia-like viruses have been isolated from human and cattle infections. This review examines the ability of potentially pathogenic orthopoxviruses, including feral versions of vaccinia virus vaccine, to persist in nature and re-emerge for reasons we do not yet understand.
Topics: Animals; Developing Countries; Humans; Molecular Sequence Data; Orthopoxvirus; Poxviridae Infections; Viral Vaccines; Zoonoses
PubMed: 19738346
DOI: 10.3855/jidc.258 -
BMC Biology Oct 2023After the eradication of smallpox in China in 1979, vaccination with the vaccinia virus (VACV) Tiantan strain for the general population was stopped in 1980. As the...
BACKGROUND
After the eradication of smallpox in China in 1979, vaccination with the vaccinia virus (VACV) Tiantan strain for the general population was stopped in 1980. As the monkeypox virus (MPXV) is rapidly spreading in the world, we would like to investigate whether the individuals with historic VACV Tiantan strain vaccination, even after more than 40 years, could still provide ELISA reactivity and neutralizing protection; and whether the unvaccinated individuals have no antibody reactivity against MPXV at all.
RESULTS
We established serologic ELISA to measure the serum anti-MPXV titer by using immunodominant MPXV surface proteins, A35R, B6R, A29L, and M1R. A small proportion of individuals (born before 1980) with historic VACV Tiantan strain vaccination exhibited serum ELISA cross-reactivity against these MPXV surface proteins. Consistently, these donors also showed ELISA seropositivity and serum neutralization against VACV Tiantan strain. However, surprisingly, some unvaccinated young adults (born after 1980) also showed potent serum ELISA activity against MPXV proteins, possibly due to their past infection by some self-limiting Orthopoxvirus (OPXV).
CONCLUSIONS
We report the serum ELISA cross-reactivity against MPXV surface protein in a small proportion of individuals both with and without VACV Tiantan strain vaccination history. Combined with our serum neutralization assay against VACV and the recent literature about mice vaccinated with VACV Tiantan strain, our study confirmed the anti-MPXV cross-reactivity and cross-neutralization of smallpox vaccine using VACV Tiantan strain. Therefore, it is necessary to restart the smallpox vaccination program in high risk populations.
Topics: Animals; Humans; Mice; Young Adult; Antibody Formation; East Asian People; Membrane Proteins; Monkeypox virus; Smallpox; Vaccination; Vaccinia virus; Smallpox Vaccine; Cross Reactions; China
PubMed: 37784185
DOI: 10.1186/s12915-023-01699-8 -
Human Vaccines & Immunotherapeutics Jul 2012In 1796, Edward Jenner introduced the concept of vaccination with cowpox virus, an Orthopoxvirus within the family Poxviridae that elicits cross protective immunity... (Review)
Review
In 1796, Edward Jenner introduced the concept of vaccination with cowpox virus, an Orthopoxvirus within the family Poxviridae that elicits cross protective immunity against related orthopoxviruses, including smallpox virus (variola virus). Over time, vaccinia virus (VACV) replaced cowpox virus as the smallpox vaccine, and vaccination efforts eventually led to the successful global eradication of smallpox in 1979. VACV has many characteristics that make it an excellent vaccine and that were crucial for the successful eradication of smallpox, including (1) its exceptional thermal stability (a very important but uncommon characteristic in live vaccines), (2) its ability to elicit strong humoral and cell-mediated immune responses, (3) the fact that it is easy to propagate, and (4) that it is not oncogenic, given that VACV replication occurs exclusively within the host cell cytoplasm and there is no evidence that the viral genome integrates into the host genome. Since the eradication of smallpox, VACV has experienced a renaissance of interest as a viral vector for the development of recombinant vaccines, immunotherapies, and oncolytic therapies, as well as the development of next-generation smallpox vaccines. This revival is mainly due to the successful use and extensive characterization of VACV as a vaccine during the smallpox eradication campaign, along with the ability to genetically manipulate its large dsDNA genome while retaining infectivity and immunogenicity, its wide mammalian host range, and its natural tropism for tumor cells that allows its use as an oncolytic vector. This review provides an overview of new uses of VACV that are currently being explored for the development of vaccines, immunotherapeutics, and oncolytic virotherapies.
Topics: Drug Carriers; Genetic Vectors; Host Specificity; Humans; Oncolytic Viruses; Vaccines, Synthetic; Vaccinia virus; Viral Vaccines
PubMed: 22777090
DOI: 10.4161/hv.21080 -
Antiviral Research Jul 2021Decades after the eradication of smallpox and the discontinuation of routine smallpox vaccination, over half of the world's population is immunologically naïve to...
Decades after the eradication of smallpox and the discontinuation of routine smallpox vaccination, over half of the world's population is immunologically naïve to variola virus and other orthopoxviruses (OPXVs). Even in those previously vaccinated against smallpox, protective immunity wanes over time. As such, there is a concomitant increase in the incidence of human OPXV infections worldwide. To identify novel antiviral compounds with potent anti-OPXV potential, we characterized the inhibitory activity of PAV-866 and other methylene blue derivatives against the prototypic poxvirus, vaccinia virus (VACV). These compounds inactivated virions prior to infection and consequently inhibited viral binding, fusion and entry. The compounds exhibited strong virucidal activity at non-cytotoxic concentrations, and inhibited VACV infection when added before, during or after viral adsorption. The compounds were effective against other OPXVs including monkeypox virus, cowpox virus and the newly identified Akhmeta virus. Altogether, these findings reveal a novel mode of inhibition that has not previously been demonstrated for small molecule compounds against VACV. Additional studies are in progress to determine the in vivo efficacy of these compounds against OPXVs and further characterize the anti-viral effects of these derivatives.
Topics: Antiviral Agents; Cell Line; Cowpox virus; HeLa Cells; Humans; Methylene Blue; Monkeypox virus; Orthopoxvirus; Vaccinia virus; Virus Attachment
PubMed: 33992710
DOI: 10.1016/j.antiviral.2021.105086 -
Viruses Apr 2015Monkeypox is a zoonotic disease caused by a virus member of the genus Orthopoxvirus and is endemic to Central and Western African countries. Previous work has identified...
Monkeypox is a zoonotic disease caused by a virus member of the genus Orthopoxvirus and is endemic to Central and Western African countries. Previous work has identified two geographically disjuct clades of monkeypox virus based on the analysis of a few genomes coupled with epidemiological and clinical analyses; however, environmental and geographic causes of this differentiation have not been explored. Here, we expand previous phylogenetic studies by analyzing a larger set of monkeypox virus genomes originating throughout Sub-Saharan Africa to identify possible biogeographic barriers associated with genetic differentiation; and projected ecological niche models onto environmental conditions at three periods in the past to explore the potential role of climate oscillations in the evolution of the two primary clades. Analyses supported the separation of the Congo Basin and West Africa clades; the Congo Basin clade shows much shorter branches, which likely indicate a more recent diversification of isolates within this clade. The area between the Sanaga and Cross Rivers divides the two clades and the Dahomey Gap seems to have also served as a barrier within the West African clade. Contraction of areas with suitable environments for monkeypox virus during the Last Glacial Maximum, suggests that the Congo Basin clade of monkeypox virus experienced a severe bottleneck and has since expanded its geographic range.
Topics: Africa South of the Sahara; Animals; Cluster Analysis; DNA, Viral; Ecosystem; Humans; Molecular Sequence Data; Mpox (monkeypox); Monkeypox virus; Phylogeography; Sequence Analysis, DNA; Sequence Homology
PubMed: 25912718
DOI: 10.3390/v7042168 -
Frontiers in Cellular and Infection... 2022Starting from mid-May 2022, cases of human monkeypox started to rise in several non-endemic countries. By mid-July, more than 17000 confirmed/suspect cases have been... (Review)
Review
Starting from mid-May 2022, cases of human monkeypox started to rise in several non-endemic countries. By mid-July, more than 17000 confirmed/suspect cases have been reported by at least 82 countries worldwide, with a regular incremental trend. In order to contain the disease diffusion, risk evaluation is crucial to undertake informed decisions and effective communication campaigns. However, since orthopoxvirus infections so far have attracted low attention, due to the eradication of smallpox 40 years ago, and to the confinement of human monkeypox almost exclusively to endemic areas, several unresolved issues concerning natural history, ecology and pathogenesis remain. To this respect, we identified some open questions and reviewed the relevant literature on monkeypoxvirus and/or related orthopoxviruses. The results will be discussed in the perspective of their relevance to public health decisions, particularly those related to non-pharmacological interventions.
Topics: Disease Outbreaks; Humans; Mpox (monkeypox); Monkeypox virus; Public Health; Smallpox
PubMed: 36204640
DOI: 10.3389/fcimb.2022.1005955 -
Viruses Aug 2018Taterapox virus (TATV) is phylogenetically the closest related virus to variola-the etiological agent of smallpox. Despite the similarity, few studies have evaluated the...
Taterapox virus (TATV) is phylogenetically the closest related virus to variola-the etiological agent of smallpox. Despite the similarity, few studies have evaluated the virus. In vivo, TATV can infect several animals but produces an inapparent infection in wild-type mice; however, TATV does cause morbidity and mortality in some immunocompromised strains. We employed in vitro techniques to compare TATV to ectromelia (ECTV) and vaccinia (VACV) viruses. Both ECTV and TATV replicate efficiently in primate cell lines but TATV replicates poorly in murine cells lines. Furthermore, TATV induces cytopathic effects, but to a lesser extent than ECTV, and changes cytoskeletal networks differently than both ECTV and VACV. Bioinformatic studies revealed differences in several immunomodulator open reading frames that could contribute to the reduced virulence of TATV, which were supported by in vitro cytokine assays.
Topics: A549 Cells; Animals; Cell Line; Chlorocebus aethiops; Cowpox virus; Ectromelia virus; Humans; Mice; Mice, Inbred BALB C; Open Reading Frames; Orthopoxvirus; Phylogeny; Poxviridae Infections; Sequence Analysis, Protein; Spleen; Vaccinia virus; Vero Cells; Virulence
PubMed: 30158437
DOI: 10.3390/v10090463 -
PLoS Pathogens Oct 2018
Topics: Biohazard Release; Dual Use Research; Humans; Orthopoxvirus; Poxviridae Infections
PubMed: 30286197
DOI: 10.1371/journal.ppat.1007344