Multi-origins and complex transmission paths of monkeypox viruses.
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ABSTRACT:
SUBMITTER: Yuan S
PROVIDER: S-EPMC9444933 | biostudies-literature | 2022 Nov-Dec
REPOSITORIES: biostudies-literature
Publications
Multi-origins and complex transmission paths of monkeypox viruses.
Yuan Shu S Jiang Si-Cong SC Zhang Zhong-Wei ZW Yang Xin-Yue XY Fu Yu-Fan YF Li Zi-Lin ZL Hu Jing J
Travel medicine and infectious disease 20220906
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Project description:Smallpox was eradicated more than 10 years ago, but infection with another Orthopoxvirus, monkeypox virus, can result in a clinical picture resembling smallpox. Human infection with monkeypox virus is extremely rare, not easily transmitted, and confined to the rain forest belt of Africa (Z. Jezek and F. Fenner, p. 81-102, in Human Monkeypox, 1988). Evidence that variola virus, the causative agent of smallpox, might be readily derived from monkeypox virus was presented [S. S. Marennikova and E. M. Shelukhina, Nature (London) 276:291-292, 1978; S. S. Marennikova, E. M. Shelukhina, N. N. Maltseva, and G. R. Matsevich Intervirology 11:333-340, 1979], but this was not confirmed [K. R. Dumbell and L. C. Archard, Nature (London) 286:29-32, 1980] and was subsequently discounted (J. J. Esposito, J. H. Nakano, and J. F. Obijeski, Bull. W.H.O. 63:695-703, 1985). Although enough difference between the genomes of monkeypox and variola viruses to rule out a simple interconversion has been demonstrated [K. R. Dumbell and L. C. Archard, Nature (London) 286:29-32, 1980; J. J. Esposito and J. C. Knight, Virology 143:230-251, 1985; J. J. Esposito, J. H. Nakano, and J. F. Obijeski, Bull. W.H.O. 63:695-703, 1985; M. Mackett and L. C. Archard, J. Gen. Virol. 45:683-701, 1979], the possibility that monkeypox virus was a more remote ancestor of variola virus remained. We have now identified a sequence in monkeypox virus DNA which is a homolog of a 1,065-bp open reading frame in the conserved region of the variola virus genome but which has multiple deletions. This is strong evidence that monkeypox virus is not ancestral to variola virus and strengthens confidence in the long-term success of smallpox eradication.
| S-EPMC240470 | biostudies-other
Project description:Monkeypox virus (MPV) causes a human disease which resembles smallpox but with a lower person-to-person transmission rate. To determine the genetic relationship between the orthopoxviruses causing these two diseases, we sequenced the 197-kb genome of MPV isolated from a patient during a large human monkeypox outbreak in Zaire in 1996. The nucleotide sequence within the central region of the MPV genome, which encodes essential enzymes and structural proteins, was 96.3% identical with that of variola (smallpox) virus (VAR). In contrast, there were considerable differences between MPV and VAR in the regions encoding virulence and host-range factors near the ends of the genome. Our data indicate that MPV is not the direct ancestor of VAR and is unlikely to naturally acquire all properties of VAR.
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| S-EPMC9629015 | biostudies-literature
Project description:The enterically transmitted hepatitis A (HAV) and hepatitis E viruses (HEV) are the leading causes of acute viral hepatitis in humans. Despite the discovery of HAV and HEV 40-50 years ago, their evolutionary origins remain unclear. Recent discoveries of numerous nonprimate hepatoviruses and hepeviruses allow revisiting the evolutionary history of these viruses. In this review, we provide detailed phylogenomic analyses of primate and nonprimate hepatoviruses and hepeviruses. We identify conserved and divergent genomic properties and corroborate historical interspecies transmissions by phylogenetic comparisons and recombination analyses. We discuss the likely non-recent origins of human HAV and HEV precursors carried by mammals other than primates, and detail current zoonotic HEV infections. The novel nonprimate hepatoviruses and hepeviruses offer exciting new possibilities for future research focusing on host range and the unique biological properties of HAV and HEV.
| S-EPMC6280709 | biostudies-literature
Project description:Although the World Health Organization (WHO) declared global smallpox eradicated in 1980, concerns over emergent poxvirus infections have increased. Most poxvirus infections are zoonotic; exploring their genetic diversity will illuminate the genetic and evolutionary aspects of poxvirus infections, ecology, and epidemiology. In recent decades, several strains of the orthopoxvirus vaccinia virus (VACV) have been isolated throughout Brazil, including genetically distinct isolates within the same outbreak. To further investigate the diversity and origins of these viruses, we analyzed molecular data from 8 Brazilian VACV isolates and compared several genes involved in virus structure and pathogenicity. Genetic variation among isolates suggests that ancestral Brazilian VACVs existed before the beginning of the WHO smallpox eradication vaccination campaigns and that these viruses continue to circulate.
| S-EPMC2878226 | biostudies-literature
Project description:BackgroundMonkeypox (MPX) is endemic in Nigeria, but it was first reported in Adamawa state, North-Eastern Nigeria, in January 2022. There are currently 172 cases of MPX in Nigeria, with four reported deaths, and Adamawa has the second-highest case count. Therefore, this study was undertaken to evaluate the epidemiological profile of this viral disease.MethodsThis is a cross-sectional study. The skin and blood samples were screened for the presence for Monkeypox virus (MPXV) and Varicella Zoster virus (VZV) DNA by real-time PCR; the clinical diagnosis was based on symptoms of visual signs of skin lesions and other clinical symptoms from January to July 2022.ResultsA total of 33 suspected cases aged 1-57 years [26 (79%) males vs. 7 (21%) females] were screened for MPX and VZV. Twenty-four (72.7%) were positive (6.1% were MPX only, 39% were VZV only, and 27% were both MPX and VZV). Most cases of MPX (82%), VZV (69%) and MPX-VZV co-infection (78%) occurred in males. More than half (54%) of those infected were children and adolescents between 0 and 19 years. All patients experienced body rashes and itching, and other clinical symptoms included fever, headache, mouth sores, muscle aches and lymphadenopathy. Over 64 and 86% of patients had contact with livestock and rodents, respectively.ConclusionMPXV, VZV and MPXV-VZV co-infections occurred predominantly among males and children in Adamawa state, Nigeria. Given the patient contact with rodents and livestock, further research on the animal reservoir is needed to highlight the transmission of MPXV in Adamawa.
| S-EPMC9797713 | biostudies-literature
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| S-EPMC9533917 | biostudies-literature
Project description:The global outbreak of human monkeypox virus (hMPXV1) in 2022 highlighted the usefulness of dermatological manifestations for its diagnosis. Infection by the human monkeypox virus thus necessitated inclusion in the diagnostic repertoire of dermatopathology. To assess the histopathological and microscopical findings of cutaneous lesions related to hMPXV infection, we analyzed skin biopsies from patients with positive MPXV DNA polymerase chain reaction presenting with a typical course of hMPXV1 infection. The most prominent histopathological findings were ascribable to a pustular stage in which epidermal necrosis with areas of non-viable keratinocytes and a "shadow cell" appearance were evident; in some cases, the deep portion of the hair follicle and the acrosyringial epithelium were affected. The main cytopathic modifications included ballooning keratinocytes, followed by Guarnieri bodies and a ground glass appearance of the keratinocytes' nuclei, together with a dense mixed inflammatory cell infiltrate with prominent neutrophil exocytosis. Transmission electron microscopy analysis demonstrated viral particle aggregates in the cytoplasm of keratinocytes, without any involvement of the nucleus. Interestingly, we also found the presence of viral particles in infected mesenchymal cells, although to a lesser extent than in epithelial cells. Through this study, we contributed to expanding the histological and microscopic knowledge of the human mpox virus, a key step to understanding current and potential future trends of the disease, as well as of other Orthopoxvirus infections.
| S-EPMC10385849 | biostudies-literature
Project description:Notwithstanding the presence of a smallpox vaccine that is effective against monkeypox (mpox), developing a universal vaccine candidate against monkeypox virus (MPXV) is highly required as the mpox multi-country outbreak has increased global concern. MPXV, along with variola virus (VARV) and vaccinia virus (VACV), belongs to the Orthopoxvirus genus. Due to the genetic similarity of antigens in this study, we have designed a potentially universal mRNA vaccine based on conserved epitopes that are specific to these three viruses. In order to design a potentially universal mRNA vaccine, antigens A29, A30, A35, B6, and M1 were selected. The conserved sequences among the three viral species-MPXV, VACV, and VARV-were detected, and B and T cell epitopes containing the conserved elements were used for the design of the multi-epitope mRNA construct. Immunoinformatics analyses demonstrated the stability of the vaccine construct and optimal binding to MHC molecules. Humoral and cellular immune responses were induced by immune simulation analyses. Eventually, based on in silico analysis, the universal mRNA multi-epitope vaccine candidate designed in this study may have a potential protection against MPXV, VARV, and VACV that will contribute to the advancement of prevention strategies for unpredictable pandemics.
| S-EPMC10222975 | biostudies-literature
Project description:The monkeypox virus (MPX) belongs to the Orthopoxvirus genus of the Poxviridae family, is endemic in parts of Africa and causes a disease in humans similar to smallpox. The most recent outbreak of MPX is already affecting 110 countries, with 86,956 confirmed cases since May 2022 and has consequently become a focus of interest. In particular, a molecular understanding of the virus is essential to study infection processes and pathogen-host interactions, predict tropism changes, or guide drug development and drug discovery as well as vaccine development or vaccine adaptation at a very early stage. Herein, we present a study of the structural proteome of the currently circulating MPX: Our consensus analysis of 3,713 genome sequences sampled within a year after the outbreak revealed 10,580 characteristic candidate open reading frames (ORFs). A search in the non-redundant protein database reduced the number of suspected ORFs to 1,079, of which 210 are representative proteins in typical MPX reference genomes. This should serve as a collection of putative proteins within the currently spreading MPX, a compound of information that could support timely drug discovery, mutational analyses, and vaccine development. We, herein, present the so far most comprehensive structural proteome by providing atomistic 3D models of 210 proteins, generated with three state-of-the-art structure prediction methods, including a mutational analysis of the proteome, with a particular focus on the drug-binding sites of tecovirimat and brincidofovir. IMPORTANCE The 2022 outbreak of the monkeypox virus already involves, by April 2023, 110 countries with 86,956 confirmed cases and 119 deaths. Understanding an emerging disease on a molecular level is essential to study infection processes and eventually guide drug discovery at an early stage. To support this, we provide the so far most comprehensive structural proteome of the monkeypox virus, which includes 210 structural models, each computed with three state-of-the-art structure prediction methods. Instead of building on a single-genome sequence, we generated our models from a consensus of 3,713 high-quality genome sequences sampled from patients within 1 year of the outbreak. Therefore, we present an average structural proteome of the currently isolated viruses, including mutational analyses with a special focus on drug-binding sites. Continuing dynamic mutation monitoring within the structural proteome presented here is essential to timely predict possible physiological changes in the evolving virus.
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