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Viruses Apr 2023Mpox (previously known as monkeypox) is an infectious viral illness caused by the mpox virus (MPXV), an orthopoxvirus that belongs to the family . The symptoms of mpox... (Review)
Review
Mpox (previously known as monkeypox) is an infectious viral illness caused by the mpox virus (MPXV), an orthopoxvirus that belongs to the family . The symptoms of mpox in humans are similar to those of smallpox, although the mortality rate is lower. In recent years, the concern over a potential global pandemic has increased due to reports of mpox spreading across Africa and other parts of the world. Prior to this discovery, mpox was a rare zoonotic disease restricted to endemic regions of Western and Central Africa. The sudden emergence of MPXV cases in multiple regions has raised concerns about its natural evolution. This review aims to provide an overview of previously available information about MPXV, including its genome, morphology, hosts and reservoirs, and virus-host interaction and immunology, as well as to perform phylogenetic analysis on available MPXV genomes, with an emphasis on the evolution of the genome in humans as new cases emerge.
Topics: Humans; Monkeypox virus; Mpox (monkeypox); Phylogeny; Evolution, Molecular; Orthopoxvirus; Rare Diseases
PubMed: 37112975
DOI: 10.3390/v15040995 -
Cell Reports Methods Oct 2023Mpox is caused by a zoonotic virus belonging to the Orthopoxvirus genus and the Poxviridae family. In this study, we develop a recombinase polymerase amplification...
Mpox is caused by a zoonotic virus belonging to the Orthopoxvirus genus and the Poxviridae family. In this study, we develop a recombinase polymerase amplification (RPA)-coupled CRISPR-Cas12a detection assay for the mpox virus. We design and test a series of CRISPR-derived RNAs(crRNAs) targeting the conserved D6R and E9L genes for orthopoxvirus and the unique N3R and N4R genes for mpox viruses. D6R crRNA-1 exhibits the most robust activity in detecting orthopoxviruses, and N4R crRNA-2 is able to distinguish the mpox virus from other orthopoxviruses. The Cas12a/crRNA assay alone presents a detection limit of 10 copies of viral DNA, whereas coupling RPA increases the detection limit to 1-10 copies. The one-tube RPA-Cas12a assay can, therefore, detect viral DNA as low as 1 copy within 30 min and holds the promise of providing point-of-care detection for mpox viral infection.
Topics: Humans; Recombinases; CRISPR-Cas Systems; Monkeypox virus; DNA, Viral; Mpox (monkeypox); Nucleotidyltransferases; Orthopoxvirus; RNA, Guide, CRISPR-Cas Systems
PubMed: 37848032
DOI: 10.1016/j.crmeth.2023.100620 -
Emerging Infectious Diseases Dec 2022To determine a demographic overview of orthopoxvirus seroprevalence, we tested blood samples collected during 2003-2019 from France (n = 4,876), Bolivia (n = 601), Laos...
To determine a demographic overview of orthopoxvirus seroprevalence, we tested blood samples collected during 2003-2019 from France (n = 4,876), Bolivia (n = 601), Laos (n = 657), and Mali (n = 255) for neutralizing antibodies against vaccinia virus. In addition, we tested 4,448 of the 4,876 samples from France for neutralizing antibodies against cowpox virus. We confirmed extensive cross-immunity between the 2 viruses. Seroprevalence of antibodies was <1% in Bolivia, <5% in Laos, and 17.25% in Mali. In France, we found low prevalence of neutralizing antibodies in persons who were unvaccinated and vaccinated for smallpox, suggesting immunosenescence occurred in vaccinated persons, and smallpox vaccination compliance declined before the end of compulsory vaccination. Our results suggest that populations in Europe, Africa, Asia, and South America are susceptible to orthopoxvirus infections, which might have precipitated the emergence of orthopoxvirus infections such as the 2022 spread of monkeypox in Europe.
Topics: Humans; Orthopoxvirus; Smallpox; Seroepidemiologic Studies; Bolivia; Laos; Mali; Antibodies, Neutralizing; Communicable Diseases
PubMed: 36343384
DOI: 10.3201/eid2812.221136 -
Viruses Mar 2015The question of the origin of smallpox, one of the major menaces to humankind, is a constant concern for the scientific community. Smallpox is caused by the agent... (Review)
Review
The question of the origin of smallpox, one of the major menaces to humankind, is a constant concern for the scientific community. Smallpox is caused by the agent referred to as the variola virus (VARV), which belongs to the genus Orthopoxvirus. In the last century, smallpox was declared eradicated from the human community; however, the mechanisms responsible for the emergence of new dangerous pathogens have yet to be unraveled. Evolutionary analyses of the molecular biological genomic data of various orthopoxviruses, involving a wide range of epidemiological and historical information about smallpox, have made it possible to date the emergence of VARV. Comparisons of the VARV genome to the genomes of the most closely related orthopoxviruses and the examination of the distribution their natural hosts' ranges suggest that VARV emerged 3000 to 4000 years ago in the east of the African continent. The VARV evolution rate has been estimated to be approximately 2 × 10-6 substitutions/site/year for the central conserved genomic region and 4 × 10-6 substitutions/site/year for the synonymous substitutions in the genome. Presumably, the introduction of camels to Africa and the concurrent changes to the climate were the particular factors that triggered the divergent evolution of a cowpox-like ancestral virus and thereby led to the emergence of VARV.
Topics: Africa, Eastern; Evolution, Molecular; Humans; Mutation Rate; Variola virus
PubMed: 25763864
DOI: 10.3390/v7031100 -
Viruses Aug 2017Cells have multiple means to induce apoptosis in response to viral infection. Poxviruses must prevent activation of cellular apoptosis to ensure successful replication.... (Review)
Review
Cells have multiple means to induce apoptosis in response to viral infection. Poxviruses must prevent activation of cellular apoptosis to ensure successful replication. These viruses devote a substantial portion of their genome to immune evasion. Many of these immune evasion products expressed during infection antagonize cellular apoptotic pathways. Poxvirus products target multiple points in both the extrinsic and intrinsic apoptotic pathways, thereby mitigating apoptosis during infection. Interestingly, recent evidence indicates that poxviruses also hijack cellular means of eliminating apoptotic bodies as a means to spread cell to cell through a process called apoptotic mimicry. Poxviruses are the causative agent of many human and veterinary diseases. Further, there is substantial interest in developing these viruses as vectors for a variety of uses including vaccine delivery and as oncolytic viruses to treat certain human cancers. Therefore, an understanding of the molecular mechanisms through which poxviruses regulate the cellular apoptotic pathways remains a top research priority. In this review, we consider anti-apoptotic strategies of poxviruses focusing on three relevant poxvirus genera: , , and . All three genera express multiple products to inhibit both extrinsic and intrinsic apoptotic pathways with many of these products required for virulence.
Topics: Animals; Apoptosis; Caspases; Host-Pathogen Interactions; Humans; Immune Evasion; Leporipoxvirus; Molluscipoxvirus; Orthopoxvirus; Poxviridae; Poxviridae Infections; Signal Transduction; Viral Proteins; Virulence; Virus Replication
PubMed: 28786952
DOI: 10.3390/v9080215 -
Viruses Mar 2018Bovine vaccinia (BV), caused by (VACV), is a zoonosis characterized by exanthematous lesions in the teats of dairy cows and the hands of milkers and is an important... (Review)
Review
Bovine vaccinia (BV), caused by (VACV), is a zoonosis characterized by exanthematous lesions in the teats of dairy cows and the hands of milkers and is an important public health issue. Severe VACV-induced lesions in the teats and udder of cows and buffaloes could lead to mastitis and other secondary infections, thereby reducing productivity and resulting in economic losses to the dairy industry. In Brazil, BV re-emerged in the late 1990s and is now endemic in most of the Brazilian territory. In the last 15 years, much effort has been made to know more about this disease and its epidemiology, etiologic agents, and interactions with the host and the environment. In this review, we describe the known dynamics of VACV infection in cattle and the viral shedding routes, as well as the relevance of BV for animal and public health.
Topics: Animals; Brazil; Cattle; Cattle Diseases; Humans; Public Health; Vaccinia; Vaccinia virus; Virus Shedding; Zoonoses
PubMed: 29522489
DOI: 10.3390/v10030120 -
Trends in Pharmacological Sciences Jan 2023A multicountry outbreak of monkeypox has gained global attention. Basic research including structural and immunological investigation on monkeypox virus (MPXV) is...
A multicountry outbreak of monkeypox has gained global attention. Basic research including structural and immunological investigation on monkeypox virus (MPXV) is central to design effective solutions of treatment with antivirals and appropriate vaccines. We summarize some information about this virus and its re-emergence and the current vaccines that are proposed to limit its spread and present some possible avenues for developing new vaccines.
Topics: Humans; Mpox (monkeypox); Monkeypox virus
PubMed: 36563658
DOI: 10.1016/j.tips.2022.10.005 -
International Journal of Molecular... Dec 2022Monkeypox infection is caused by a virus of the genus , a member of the family. Monkeypox virus is transmitted from individual to individual through contact with... (Review)
Review
Monkeypox infection is caused by a virus of the genus , a member of the family. Monkeypox virus is transmitted from individual to individual through contact with lesions, body fluids, and respiratory droplets. The infection caused by monkeypox is usually a self-limited disease with mild symptoms lasting 2 to 4 weeks. Monkeypox typically presents with fever, rash, and enlarged lymph nodes. New vaccines have recently been authorized for the prevention of monkeypox infection, whereas there are no specific pharmacological antiviral treatments for monkeypox infection. However, because the viruses which cause adult smallpox and monkeypox are similar, antiviral drugs developed in the past have also shown efficacy against monkeypox. In this review, we highlight the in vitro and clinical evidence found in the literature on the efficacy and safety of pharmacological agents with antiviral activity against monkeypox infection and the different regulatory aspects of countries.
Topics: Adult; Humans; Mpox (monkeypox); Antiviral Agents; Monkeypox virus; Body Fluids
PubMed: 36555584
DOI: 10.3390/ijms232415941 -
Immunity Feb 2021The vaccine strain against smallpox, vaccinia virus (VACV), is highly immunogenic yet causes relatively benign disease. These attributes are believed to be caused by...
The vaccine strain against smallpox, vaccinia virus (VACV), is highly immunogenic yet causes relatively benign disease. These attributes are believed to be caused by gene loss in VACV. Using a targeted small interfering RNA (siRNA) screen, we identified a viral inhibitor found in cowpox virus (CPXV) and other orthopoxviruses that bound to the host SKP1-Cullin1-F-box (SCF) machinery and the essential necroptosis kinase receptor interacting protein kinase 3 (RIPK3). This "viral inducer of RIPK3 degradation" (vIRD) triggered ubiquitination and proteasome-mediated degradation of RIPK3 and inhibited necroptosis. In contrast to orthopoxviruses, the distantly related leporipoxvirus myxoma virus (MYXV), which infects RIPK3-deficient hosts, lacks a functional vIRD. Introduction of vIRD into VACV, which encodes a truncated and defective vIRD, enhanced viral replication in mice. Deletion of vIRD reduced CPXV-induced inflammation, viral replication, and mortality, which were reversed in RIPK3- and MLKL-deficient mice. Hence, vIRD-RIPK3 drives pathogen-host evolution and regulates virus-induced inflammation and pathogenesis.
Topics: Animals; Cowpox; Cowpox virus; Evolution, Molecular; HEK293 Cells; Host-Pathogen Interactions; Humans; Inflammation; Mice; Mice, Knockout; Necroptosis; Orthopoxvirus; Phylogeny; Protein Kinases; Proteolysis; RNA, Small Interfering; Receptor-Interacting Protein Serine-Threonine Kinases; Sequence Analysis, RNA; Vaccinia virus; Viral Proteins; Virus Replication
PubMed: 33444549
DOI: 10.1016/j.immuni.2020.11.020 -
Nature Communications Apr 2024The 2023 monkeypox (mpox) epidemic was caused by a subclade IIb descendant of a monkeypox virus (MPXV) lineage traced back to Nigeria in 1971. Person-to-person...
The 2023 monkeypox (mpox) epidemic was caused by a subclade IIb descendant of a monkeypox virus (MPXV) lineage traced back to Nigeria in 1971. Person-to-person transmission appears higher than for clade I or subclade IIa MPXV, possibly caused by genomic changes in subclade IIb MPXV. Key genomic changes could occur in the genome's low-complexity regions (LCRs), which are challenging to sequence and are often dismissed as uninformative. Here, using a combination of highly sensitive techniques, we determine a high-quality MPXV genome sequence of a representative of the current epidemic with LCRs resolved at unprecedented accuracy. This reveals significant variation in short tandem repeats within LCRs. We demonstrate that LCR entropy in the MPXV genome is significantly higher than that of single-nucleotide polymorphisms (SNPs) and that LCRs are not randomly distributed. In silico analyses indicate that expression, translation, stability, or function of MPXV orthologous poxvirus genes (OPGs), including OPG153, OPG204, and OPG208, could be affected in a manner consistent with the established "genomic accordion" evolutionary strategies of orthopoxviruses. We posit that genomic studies focusing on phenotypic MPXV differences should consider LCR variability.
Topics: Humans; Monkeypox virus; Genomics; Orthopoxvirus; Mpox (monkeypox); Poxviridae
PubMed: 38637500
DOI: 10.1038/s41467-024-46949-7