Monkeypox virus

Monkeypox virus (MPV, MPXV, or hMPXV) is a species of double-stranded DNA virus that causes monkeypox in humans and other mammals. The genome is approximately 190 kb.[1] Monkeypox virus a orthopoxvirus which makes it closely related to the variola (VARV), cowpox (CPX), and vaccinia (VACV) viruses. It is not a direct ancestor to, nor a direct descendant of, the variola virus, which causes smallpox. The clinical presentation of Monkeypox is similar to smallpox but with a milder rash and lower mortality rate.[2][3][4]The virus is transmissible between animals and humans, by direct contact to the lesions or bodily fluids.[5]

Monkeypox virus
Colorized transmission electron micrograph of monkeypox particles (teal) found within an infected cell (brown), cultured in the laboratory.
Virus classification
(unranked): Virus
Realm: Varidnaviria
Kingdom: Bamfordvirae
Phylum: Nucleocytoviricota
Class: Pokkesviricetes
Order: Chitovirales
Family: Poxviridae
Genus: Orthopoxvirus
Species:
Monkeypox virus
Clades
  • Clade I (Congo Basin)
  • Clade II (West African)
    • Clade IIa
    • Clade IIb

Monkeypox was given its name after being isolated from monkeys; however, the majority of the carriers of this virus are rodents.

Variation in virulence of the virus has been observed in isolates from Central Africa, where strains are more virulent than those from Western Africa.[2] The two areas have distinct clades of the virus, termed clade I, formerly the Congo Basin (Central African) clade, and clade II, formerly the West African clade.[6]


Comparison of monkeypox, HIV, SARS CoV-2, and polio viruses' size. Membranes and membrane-bound proteins are in purple, capsids are in dark blue, and genomes and nucleoid-associated proteins are in turquoise.

Virology

Classification

MPV is part of the genus Orthopoxvirus, belonging to the Poxviridae family, which have been listed by the WHO as diseases with epidemic or pandemic potential.[7]

Structure and genome

The monkeypox virus, like other poxviruses, is oval shaped, with a lipoprotein outer membrane. The outer membrane protects the enzymes, DNA, and transcription factors of the virus. [8]

Genome of the monkeypox virus is round 200kb which codes for approximately 200 proteins. It has double stranded DNA which presents in a linear shape with covalently closed hairpin ends; the 3’ and 5’ ends are not free.[9] Similar to other poxviruses, the irons of monkey pox have large oval shaped envelopes. Within each viiron there is a core which holds the genome along with the enzymes that assist in dissolving the protein coat and replication.[10]

Colorized transmission electron micrograph of monkeypox virus particles (green)

Replication and life cycle

As an Orthopoxvirus, MPV replication occurs entirely in the cell cytoplasm within 'factories'- created from the host rough endoplasmic reticulum (ER)- where viral mRNA transcription and translation also take place.[11][12] Translation of mRNA into structural virions occurs using the host ribosomes.[11] Gene expression begins when MPV releases viral proteins and enzymatic factors that disable the cell.[13] Protein synthesis allows for the ER membrane of the factory to dismantle, while small membranes will appear to encapsulate the genomes of new virions.[13][11] DNA concatemers process the genomes, which appear in new virions, along with other enzymes, and genetic information needed for the replication cycle to occur. [13]

Transmission

The virus can spread both from animal to human and from human to human. Infection from animal to human can occur via an animal bite or by direct contact with an infected animal's bodily fluids. The virus can spread from human to human by both direct contact with the infectious rash, scabs, or body fluids, or indirectly by touching items (such as clothing or linens) that previously touched the infectious rash or body fluids or by respiratory secretions during prolonged, face-to-face contact, or during intimate physical contact, such as kissing, cuddling, or sex. Pregnant women can spread the virus to their fetus through the placenta.[14]

The incubation period is between 10 and 14 days. Prodromal symptoms include swelling of lymph nodes, muscle pain, headache, fever, prior to the emergence of the rash.[15]

Immune system interaction

Pox viruses have mechanisms to evade the hosts' innate and adaptive immune systems. When infected human fibroblast cells have been observed to show cytopathic changes, but gene expression of the host cell remains unchanged. Interferon produced by human fibroblast cells were not sufficient to slow viral replication.[16] The Monkeypox virus gene BR-209 is an interleukin-1β (IL-1β) inhibitor that prevents interaction with the receptor. [17] The viral complement control protein (CCP), also known as MOPICE, a virulence factor, allows the virus to evade neutralization, opsonization, viral particle lysis, and phagocytosis. [18]

Variants and clades

The virus is subclassified into two main clades, the Central African/Congo Basin clade (CA) and the West African clade (WA).[19] The World Health Organization uses Roman numerals to denote each clade and a lowercase Latin script letter for subclades.[20]

At the protein level, the CA clade and WA clade share 170 orthologs, and their transcriptional regulatory sequences show no significant differences.[19] Both clades have 53 common virulence genes, which contain different types of amino acid changes. 121 of the amino acid changes in the virulence genes are silent, while 61 are conservative, and 93 are non-conservative.[19]

Both clades vary in virulence, with the CA clade having more human-human transmission, and having a higher mortality rate in non-vaccinated people.[19] The WA clade was thought to be less transmissible between humans.[19] The 2022 Monkeypox outbreak was caused by the WA clade of the virus.[21]

Clades and subclades of Monkeypox virus
Name[6] Former names[6] Nations[22][23] Case fatality rate (CFR)[24]
Clade I Congo Basin

Central African
  •  Cameroon
  •  Central African Republic
  •  Democratic Republic of the Congo
  •  Gabon
  •  Republic of the Congo
  •  South Sudan
 ~10.6%
Clade II Clade IIa West African
  •  Benin
  •  Cameroon
  •  Cote d'Ivoire
  •  Liberia
  •  Nigeria
  •  Sierra Leone
 ~3.6%
Clade IIb See 2022 monkeypox outbreak § Cases per country and territory

Distribution
Further information: Monkeypox § Epidemiology
A map of the spread of the monkeypox virus globally.
  Endemic West African clade
  Endemic Congo Basin clade
  Both clades recorded
  West African clade outbreak in 2022

Monkeypox virus is carried by various animals including primates.[25] It was first identified by Preben von Magnus in Copenhagen, Denmark, in 1958 in crab-eating macaque monkeys (Macaca fascicularis) being used as laboratory animals.[26] The 2003 outbreak in the United States was traced to prairie dogs infected from an imported Gambian pouched rat from Ghana.[27]

Monkeypox virus causes disease in both primates and in other animals. The virus is mainly found in tropical rainforest regions of Central and West Africa.[28] The virus is mainly found in the tropical forests of Central Africa and West Africa.[28] It was first discovered in monkeys in 1958, and in humans in 1970. Between 1970 and 1986, over 400 cases in humans were reported. Small viral outbreaks with secondary human-to-human infection occur routinely in equatorial Central and West Africa.[29] The primary route of infection is thought to be contact with the infected animals or their bodily fluids.[29] The first reported outbreak outside Africa occurred in 2003 in the Midwestern United States in Illinois, Indiana, and Wisconsin, with one occurrence in New Jersey. A significant outbreak in Nigeria occurred in 2017.[30]

See also

References
  1. "Factsheet for health professionals on monkeypox". European Centre for Disease Prevention and Control. Retrieved 2022-10-09.
  2. Breman JG, Steniowski MV, Zanotto E, Gromyko AI, Arita I (1980). "Human monkeypox, 1970-79". Bulletin of the World Health Organization. 58 (2): 165–182. PMC 2395797. PMID 6249508.
  3. Alkhalil A, Hammamieh R, Hardick J, Ichou MA, Jett M, Ibrahim S (July 2010). "Gene expression profiling of monkeypox virus-infected cells reveals novel interfaces for host-virus interactions". Virology Journal. 7: 173. doi:10.1186/1743-422X-7-173. PMC 2920256. PMID 20667104.
  4. Shchelkunov SN, Totmenin AV, Safronov PF, Mikheev MV, Gutorov VV, Ryazankina OI, et al. (June 2002). "Analysis of the monkeypox virus genome". Virology. 297 (2): 172–194. doi:10.1006/viro.2002.1446. PMC 9534300. PMID 12083817.
  5. CDC (2022-10-18). "Monkeypox in the U.S." Centers for Disease Control and Prevention. Retrieved 2022-10-26.
  6. "Monkeypox: experts give virus variants new names". www.who.int. Retrieved 2022-08-19.
  7. Lansiaux, Edouard; Jain, Nityanand; Laivacuma, Sniedze; Reinis, Aigars (2022-12-01). "The virology of human monkeypox virus (hMPXV): A brief overview". Virus Research. 322: 198932. doi:10.1016/j.virusres.2022.198932. ISSN 0168-1702.
  8. Alakunle E, Moens U, Nchinda G, Okeke MI (November 2020). "Monkeypox Virus in Nigeria: Infection Biology, Epidemiology, and Evolution". Viruses. 12 (11): 1257. doi:10.3390/v12111257. PMC 7694534. PMID 33167496.
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  10. "Monkeypox: What We Do and Don't Know About Recent Outbreaks". ASM.org. Retrieved 2022-10-21.
  11. "Monkeypox: What We Do and Don't Know About Recent Outbreaks". ASM.org. Retrieved 2022-10-26.
  12. Moss, B. (2013-07-09). "Poxvirus DNA Replication". Cold Spring Harbor Perspectives in Biology. 5 (9): a010199–a010199. doi:10.1101/cshperspect.a010199. ISSN 1943-0264.
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  15. "Questions and Answers About Monkeypox". Centers for Disease Control and Prevention (CDC). Retrieved 2013-06-15.
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  17. Weaver, Jessica R.; Isaacs, Stuart N. (Oct 2008). "Monkeypox virus and insights into its immunomodulatory proteins". Immunological reviews. 225: 96–113. doi:10.1111/j.1600-065X.2008.00691.x. ISSN 0105-2896. PMC 2567051. PMID 18837778.
  18. Hudson, Paul N.; Self, Joshua; Weiss, Sonja; Braden, Zachary; Xiao, Yuhong; Girgis, Natasha M.; Emerson, Ginny; Hughes, Christine; Sammons, Scott A.; Isaacs, Stuart N.; Damon, Inger K.; Olson, Victoria A. (2012). "Elucidating the role of the complement control protein in monkeypox pathogenicity". PloS One. 7 (4): e35086. doi:10.1371/journal.pone.0035086. ISSN 1932-6203. PMC 3322148. PMID 22496894.
  19. Lansiaux E, Jain N, Laivacuma S, Reinis A (September 2022). "The virology of human monkeypox virus (hMPXV): A brief overview". Virus Research. 322: 198932. doi:10.1016/j.virusres.2022.198932. PMC 9534104. PMID 36165924.
  20. "Monkeypox: experts give virus variants new names". www.who.int. Retrieved 2022-08-19.
  21. Minhaj FS, Ogale YP, Whitehill F, Schultz J, Foote M, Davidson W, et al. (June 2022). "Monkeypox Outbreak - Nine States, May 2022". MMWR. Morbidity and Mortality Weekly Report. 71 (23): 764–769. doi:10.15585/mmwr.mm7123e1. PMC 9181052. PMID 35679181.
  22. "Monkeypox". www.who.int. Retrieved 2022-08-19.
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  29. Meyer H, Perrichot M, Stemmler M, Emmerich P, Schmitz H, Varaine F, et al. (August 2002). "Outbreaks of disease suspected of being due to human monkeypox virus infection in the Democratic Republic of Congo in 2001". Journal of Clinical Microbiology. 40 (8): 2919–2921. doi:10.1128/JCM.40.8.2919-2921.2002. PMC 120683. PMID 12149352.
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