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"Monkeypox protein database"
Monkeypox virus
Monkeypox virus (MPXV) is a large virus, the 197-kb DNA genome of which consists of two linear double-stranded strands within a dumbbell-shaped inner core and an outer envelope around it . MPXV encodes 209 predicted open reading frames . A highly conserved centric region in the MPXV genome has encoding genes for structural proteins, necessary enzymes, and genes involved in viral replication . Variable terminal ends of the genome encode genes related to host range, viral defense, and viral/host interactions . Hairpin loops covalently connect inverted terminal repeats (ITRs) at the distal extremities of the genome . Virion entrance into the host cell by fusion with the plasma or endocytic membrane marks the start of the viral life cycle. Replication occurs in the cytoplasm within membrane-bound foci known as viral "factories" upon uncoating. Each cell may produce about 10,000 genomes, but half end up enclosed into virions .
Based on their geographic origins, two primary MPXV clades have been identified phylogenetically: the Congo Basin and West African. These clades are distinguished by their considerable disparities in case fatality rates (>10% and <1%, respectively), which can be attributed to a few different virulence genes.
Monkeypox on wrist and palm. The photograph depicts the wrist and palm of an individual afflicted with monkeypox, showcasing the characteristics of papular and blister-stage lesions before scab formation (Photo credit: Nigeria Centre for Disease Control.)
Map showing worldwide distribution of MPXV cases till 16 Nov 2022.
Map showing worldwide distribution of MPXV cases till 16 Nov 2022. The map has been created by using data wrapper software (Photo credit: Thakur, M., Das, P., Sobti, R. C., & Kaur, T. (2023). Human monkeypox: epidemiology, transmission, pathogenesis, immunology, diagnosis and therapeutics. Molecular and Cellular Biochemistry, 478(9), 2097-2110.)
Timeline of outbreaks
https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON385
https://www.who.int/news-room/fact-sheets/detail/monkeypox
https://www.cdc.gov/poxvirus/monkeypox/outbreak/us-outbreaks.html
Source: American Society for Microbiology
1958: mpox virus is first discovered among laboratory monkeys who exhibited pox-like disease.
1970: the first human case of mpox is reported in the Democratic Republic of Congo (DRC) when a 9-month-old boy was found to be infected.
Following the first documented human case, mpox is reported in 11 different African countries.
The disease is considered endemic to Cameroon, the Central African Republic, DRC, Gabon, Ghana, Cote D’Ivoire, Liberia, Nigeria, the Republic of the Congo and Sierra Leone.
2003: mpox is first reported in the U.S. Cases in non-endemic countries have been historically rare.
Jan 1-Sept. 13, 2020: approximately 4,594 suspected global cases of mpox and 171 deaths related to the virus are reported.
May 2022: reports of mpox outbreaks in non-endemic countries begin to circulate.
June 30, 2022: there are almost 400 confirmed cases of mpox in the U.S. (the largest outbreak in the country since 2003), nearly 1,200 cases reported in the U.K. and at least 29 other non-endemic countries reporting mpox cases.
Dec. 7, 2023: CDC issues health advisory about the occurrence and geographic spread of clade I Monkeypox virus (MPXV) in the Democratic Republic of the Congo (DRC).
Jan. 2023-Aug. 7, 2024: DRC reports the largest number of suspected cases of clade I MPXV ever annually on record.
July 2024: Burundi, Rwanda, and Uganda report confirmed cases of mpox.
Aug. 7, 2024: CDC issue health advisory to provide additional info about the mpox outbreak in the DRC.
Aug. 14, 2024: WHO determines that the growing number of mpox cases constitutes a public health emergency of international concern.
The epidemiological characteristics, pathogenesis, clinical diagnosis, and treatment of Mpox.
(a) The transmission of Mpox occurs through animal-to-animal, animal-to-human, and human-to-human routes. (b) Clinical symptoms typically manifest after Mpox infection. (c) Symptoms of Mpox infection may vary based on the immune status and clinical treatment options and clinical treatment options are listed. (Photo credit: Lu, J., Xing, H., Wang, C., Tang, M., Wu, C., Ye, F., ... & Shen, L. (2023). Mpox (formerly monkeypox): pathogenesis, prevention, and treatment. Signal Transduction and Targeted Therapy, 8(1), 458.)
The genome structure and potential antiviral targets of Mpox virus.
The Mpox virus genome consists of a double-stranded linear DNA comprising approximately 196,858 base pairs. It consists of a central recognition region, two variable region, and two terminal inverted terminal repeats (ITRs) (Monkeypox virus strain Zaire, GenBank accession number: AF380138.1, web link: https://www.ncbi.nlm.nih.gov/nuccore/17529780). In the genome map, target genes implicated in the interaction between Mpox virus and antiviral drugs are listed. Most essential genes are located in the central region of the genome (Photo credit: Lu, J., Xing, H., Wang, C., Tang, M., Wu, C., Ye, F., ... & Shen, L. (2023). Mpox (formerly monkeypox): pathogenesis, prevention, and treatment. Signal Transduction and Targeted Therapy, 8(1), 458.)
The life cycle of Mpox virus replication in hosts and potential targets for anti-Mpox virus drugs.
The complete life cycle of Mpox virus infection: from entry into host cells to excretion. Briefly, both EEV and IMV viral particles penetrate the host membrane through membrane fusion and endocytosis. Mpox virus viral particles utilize glycosaminoglycans as host receptor. IMV particles enter the cytoplasm and are transported to the perinuclear replication factory via microtubules. The released Mpox virus genome serves as a template for DNA replication. Furthermore, IMV are enveloped by the Golgi apparatus to form IEV, and are transported to the cell surface via actin or microtubules. Part of the important drugs targeting each stage of the replication process are listed. EEV extracellular enveloped virions, IMV intracellular mature virions, IEV intracellular enveloped virions, IV immature virion (Photo credit: Lu, J., Xing, H., Wang, C., Tang, M., Wu, C., Ye, F., ... & Shen, L. (2023). Mpox (formerly monkeypox): pathogenesis, prevention, and treatment. Signal Transduction and Targeted Therapy, 8(1), 458.)
The host cell immune response after Mpox virus infection.
The Mpox induces specific and non-specific immune responses after infection. Briefly, upon entry of Mpox virus into host cells, mononuclear phagocytes and neutrophils initiate recruitment and increased proliferative infiltration, other antigen-presenting cells (such as dendritic cell) become activated, leading to the release of effector molecules and chemokines, while other cells (T cells, B cells, NK cells and the complement system) of the immune system also begin to exert their corresponding effector functions. IL interleukin, Th helper T cell, IFN Interferon, ADCC antibody-dependent cell-mediated cytotoxicity (Photo credit: Lu, J., Xing, H., Wang, C., Tang, M., Wu, C., Ye, F., ... & Shen, L. (2023). Mpox (formerly monkeypox): pathogenesis, prevention, and treatment. Signal Transduction and Targeted Therapy, 8(1), 458.)
Illustrates the signaling pathways associated with the targeted actions of certain drugs following Mpox virus infection.
Upon infection, Mpox inhibits pyroptosis, impeding the formation of inflammasomes and activation of caspase-1. This blockade prevents pyroptosis and hampers the adequate activation of the immune response against Mpox infection. However, nigericin, an activator of NLRP3 can induce pyroptosis in host cells, making it a promising candidate for an anti-Mpox drug. Moreover, tBID, a protein involved in apoptosis, is suppressed upon Mpox virus infection, thereby inhibiting both intrinsic and extrinsic apoptotic pathways and ensuring the survival of Mpox virus within host cells. This mechanism can be exploited by employing apoptosis inducers as a strategy to combat Mpox virus. Furthermore, Mpox virus infection triggers the binding of EGF and EGFR, activation downstream MAPK and MEK signaling pathways, leading to the release of inflammatory and chemotactic factors, and modulation of immune cells. That is, EGFR inhibitors like gefitinib may exhibit significant anti-Mpox activity (Photo credit: Lu, J., Xing, H., Wang, C., Tang, M., Wu, C., Ye, F., ... & Shen, L. (2023). Mpox (formerly monkeypox): pathogenesis, prevention, and treatment. Signal Transduction and Targeted Therapy, 8(1), 458.)
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