:Monkeypox virus

The monkeypox virus is a zoonotic virus belonging to the genus Orthopoxvirus, which itself is a member of the family Poxviridae (also known as the poxvirus family).{{Cite journal |last1=Harapan |first1=Harapan |last2=Ophinni |first2=Youdiil |last3=Megawati |first3=Dewi |last4=Frediansyah |first4=Andri |last5=Mamada |first5=Sukamto S. |last6=Salampe |first6=Mirnawati |last7=Bin Emran |first7=Talha |last8=Winardi |first8=Wira |last9=Fathima |first9=Raisha |last10=Sirinam |first10=Salin |last11=Sittikul |first11=Pichamon |last12=Stoian |first12=Ana M. |last13=Nainu |first13=Firzan |last14=Sallam |first14=Malik |date=2022-09-29 |title=Monkeypox: A Comprehensive Review |journal=Viruses |volume=14 |issue=10 |pages=2155 |doi=10.3390/v14102155 |doi-access=free |issn=1999-4915 |pmc=9612348 |pmid=36298710}} Of note, the Orthopoxvirus genus includes the variola virus that prior to eradication via the advent of the smallpox vaccine, was the cause of the infectious human disease known as smallpox.{{cite journal |vauthors=Babkin,I, Babkina,I |date=March 2015 |title=The Origin of the variola Virus |journal=Viruses |volume=7 |issue=3 |pages=1100–12 |doi=10.3390/v7031100 |issn=1999-4915 |pmc=4379562 |pmid=25763864 |doi-access=free}} Members of the poxvirus family, include the monkeypox virus itself have been listed by the WHO as diseases with epidemic or pandemic potential.{{cite journal |vauthors=Lansiaux E, Jain N, Laivacuma S, Reinis A |date=December 2022 |title=The virology of human monkeypox virus (hMPXV): A brief overview |journal=Virus Research |volume=322 |pages=198932 |doi=10.1016/j.virusres.2022.198932 |pmc=9534104 |pmid=36165924}} The monkeypox virus is listed as being a potentially high or severe threat pathogen in both the European Union (EU) and the United States of America.{{Cite journal |last1=Tian |first1=Deqiao |last2=Zheng |first2=Tao |date=2014-06-30 |title=Comparison and Analysis of Biological Agent Category Lists Based On Biosafety and Biodefense |journal=PLOS ONE |volume=9 |issue=6 |pages=e101163 |doi=10.1371/journal.pone.0101163 |doi-access=free |issn=1932-6203 |pmc=4076228 |pmid=24979754|bibcode=2014PLoSO...9j1163T }}{{Cite journal |last1=Sklenovská |first1=Nikola |last2=Van Ranst |first2=Marc |date=2018-09-04 |title=Emergence of Monkeypox as the Most Important Orthopoxvirus Infection in Humans |journal=Frontiers in Public Health |volume=6 |pages=241 |doi=10.3389/fpubh.2018.00241 |doi-access=free |issn=2296-2565 |pmc=6131633 |pmid=30234087}}

There are two subtypes or clades, clade{{nbsp}}I historically associated with the Congo Basin and clade{{nbsp}}II historically associated with West Africa. A global outbreak during 2022–2023 was caused by clade II.

MPV is 96.3% identical to the variola virus in regards to its coding region, but it does differ in parts of the genome which encode for virulence and host range.{{cite journal | vauthors = Shchelkunov SN, Totmenin AV, Babkin IV, Safronov PF, Ryazankina OI, Petrov NA, Gutorov VV, Uvarova EA, Mikheev MV, Sisler JR, Esposito JJ, Jahrling PB, Moss B, Sandakhchiev LS | title = Human monkeypox and smallpox viruses: genomic comparison | journal = FEBS Letters | volume = 509 | issue = 1 | pages = 66–70 | date = November 2001 | pmid = 11734207 | doi = 10.1016/S0014-5793(01)03144-1 | pmc = 9533818 | bibcode = 2001FEBSL.509...66S }} Through phylogenetic analysis, it was found that MPV is not a direct descendant of the variola virus.

File:Colorized transmission electron micrograph of monkeypox virus particles (green).jpg

The monkeypox virus, like other poxviruses, is oval, with a lipoprotein outer membrane. The outer membrane protects the enzymes, DNA, and transcription factors of the virus.{{cite journal | vauthors = Alakunle E, Moens U, Nchinda G, Okeke MI | title = Monkeypox Virus in Nigeria: Infection Biology, Epidemiology, and Evolution | journal = Viruses | volume = 12 | issue = 11 | pages = 1257 | date = November 2020 | pmid = 33167496 | pmc = 7694534 | doi = 10.3390/v12111257 | doi-access = free }} Typical DNA viruses replicate and express their genome in the nucleus of eukaryotic cells, relying heavily on the host cell's machinery. However, monkeypox viruses rely mostly on proteins encoded in their genome that allow them to replicate in the cytoplasm.{{cite journal | vauthors = Kaler J, Hussain A, Flores G, Kheiri S, Desrosiers D | title = Monkeypox: A Comprehensive Review of Transmission, Pathogenesis, and Manifestation | journal = Cureus | volume = 14 | issue = 7 | page = e26531 | date = July 2022 | pmid = 35928395 | pmc = 9345383 | doi = 10.7759/cureus.26531 | doi-access = free }}

The genome of the monkeypox virus comprises 200 kb of double-stranded DNA coding for 191 proteins.{{Cite journal |last1=Forni |first1=Diego |last2=Cagliani |first2=Rachele |last3=Molteni |first3=Cristian |last4=Clerici |first4=Mario |last5=Sironi |first5=Manuela |date=November 2022 |title=Monkeypox virus: The changing facets of a zoonotic pathogen |journal=Infection, Genetics and Evolution |volume=105 |pages=105372 |doi=10.1016/j.meegid.2022.105372 |pmc=9534092 |pmid=36202208|bibcode=2022InfGE.10505372F }}{{cite journal |vauthors=Kugelman JR, Johnston SC, Mulembakani PM, Kisalu N, Lee MS, Koroleva G, McCarthy SE, Gestole MC, Wolfe ND, Fair JN, Schneider BS, Wright LL, Huggins J, Whitehouse CA, Wemakoy EO, Muyembe-Tamfum JJ, Hensley LE, Palacios GF, Rimoin AW |date=February 2014 |title=Genomic variability of monkeypox virus among humans, Democratic Republic of the Congo |journal=Emerging Infectious Diseases |volume=20 |issue=2 |pages=232–239 |doi=10.3201/eid2002.130118 |pmc=3901482 |pmid=24457084}} Similar to other poxviruses, the virions of monkey pox have large oval envelopes. Within each virion, there is a core which holds the genome, along with the enzymes that assist in dissolving the protein coat and replication.{{Cite web |title=Monkeypox: What We Do and Don't Know About Recent Outbreaks |url=https://asm.org/Articles/2022/May/Monkeypox-What-We-Do-and-Don-t-Know-About-Recent-O |access-date=2022-10-21 |website=ASM.org |archive-date=2022-10-21 |archive-url=https://web.archive.org/web/20221021034256/https://asm.org/Articles/2022/May/Monkeypox-What-We-Do-and-Don-t-Know-About-Recent-O |url-status=live }} The center of the genome codes for genes involved in key functions such as viral transcription and assembly; genes located on the extremities of the viral genome are associated more with interactions between the virus and the host cell, such as spike protein characteristics.

Monkeypox virus is relatively large, compared to other viruses. This makes it harder for the virus to breach the host defences, such as crossing gap junctions. Furthermore, the large size makes it harder for the virus to replicate quickly and evade immune response. To evade host immune systems, and buy more time for replication, monkeypox and other orthopox viruses have evolved mechanisms to evade host immune cells.{{Cite journal |last1=Zandi |first1=Milad |last2=Shafaati |first2=Maryam |last3=Hosseini |first3=Fatemeh |date=2023-02-01 |title=Mechanisms of immune evasion of monkeypox virus |journal=Frontiers in Microbiology |volume=14 |doi=10.3389/fmicb.2023.1106247 |issn=1664-302X |pmc=9928851 |pmid=36819041 |doi-access=free }}

File:Monkeypox viruses scale.png

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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.{{Cite web |title=Monkeypox: What We Do and Don't Know About Recent Outbreaks |url=https://asm.org/Articles/2022/May/Monkeypox-What-We-Do-and-Don-t-Know-About-Recent-O |access-date=2022-10-26 |website=ASM.org |archive-date=2022-10-21 |archive-url=https://web.archive.org/web/20221021034256/https://asm.org/Articles/2022/May/Monkeypox-What-We-Do-and-Don-t-Know-About-Recent-O |url-status=live }}{{cite journal | vauthors = Moss B | title = Poxvirus DNA replication | journal = Cold Spring Harbor Perspectives in Biology | volume = 5 | issue = 9 | pages = a010199 | date = September 2013 | pmid = 23838441 | pmc = 3753712 | doi = 10.1101/cshperspect.a010199 }} The factories are also where DNA replication, gene expression, and assembly of mature virions (MV) are located.{{cite journal | vauthors = Realegeno S, Puschnik AS, Kumar A, Goldsmith C, Burgado J, Sambhara S, Olson VA, Carroll D, Damon I, Hirata T, Kinoshita T, Carette JE, Satheshkumar PS | title = Monkeypox Virus Host Factor Screen Using Haploid Cells Identifies Essential Role of GARP Complex in Extracellular Virus Formation | journal = Journal of Virology | volume = 91 | issue = 11 | pages = e00011–17 | date = June 2017 | pmid = 28331092 | pmc = 5432867 | doi = 10.1128/JVI.00011-17 }}

MPV virions (MVs) are able to bind to the cell surface with the help of viral proteins.{{cite journal | vauthors = Moss B | title = Membrane fusion during poxvirus entry | journal = Seminars in Cell & Developmental Biology | volume = 60 | issue = | pages = 89–96 | date = December 2016 | pmid = 27423915 | pmc = 5161597 | doi = 10.1016/j.semcdb.2016.07.015 }} Virus entry into the host cell plasma membrane is dependent on a neutral pH, otherwise entry occurs via a low-pH dependent endocytic route. The MV of the monkeypox virus has an Entry Fusion Complex (EFC), allowing it to enter the host cell after attachment.

The viral mRNA is translated into structural virion protein by the host ribosomes. Gene expression begins when MPV releases viral proteins and enzymatic factors that disable the cell.{{cite journal | vauthors = Alkhalil A, Hammamieh R, Hardick J, Ichou MA, Jett M, Ibrahim S | title = Gene expression profiling of monkeypox virus-infected cells reveals novel interfaces for host-virus interactions | journal = Virology Journal | volume = 7 | page = 173 | date = July 2010 | pmid = 20667104 | pmc = 2920256 | doi = 10.1186/1743-422X-7-173 | doi-access = free }} Mature virions are infectious. However, they will stay inside the cell until they are transported from the factories to the Golgi/endosomal compartment. Protein synthesis allows for the ER membrane of the factory to dismantle, while small lipid-bilayer membranes will appear to encapsulate the genomes of new virions, now extracellular viruses (EVs). The VPS52 and VPS54 genes of the GARP complex, which is important for transport, are necessary for wrapping the virus, and formation of EVs. DNA concatemers process the genomes, which appear in new virions, along with other enzymes, and genetic information needed for the replication cycle to occur. EVs are necessary for the spread of the virus from cell-to-cell and its long-distance spread.

Zoonotic transmission can occur from direct contact with the blood, bodily fluids, wounds, or mucosal lesions of infected animals whether they are dead or alive. The virus is thought to have originated in Africa where the virus has been observed in multiple animals, including rope squirrels, tree squirrels, Gambian pouched rats, dormice, and different species of monkeys. Though the natural reservoir of the monkeypox virus has not yet been established, rodents are speculated to be the most likely reservoir. Eating meat that has not been properly cooked and consuming other products of infected animals proves to be a major risk factor in the spread of infection.{{Cite web |title=Monkeypox |url=https://www.who.int/news-room/fact-sheets/detail/monkeypox |url-status=live |archive-url=https://web.archive.org/web/20220421083742/https://www.who.int/news-room/fact-sheets/detail/monkeypox |archive-date=2022-04-21 |access-date=2022-11-18 |website=World Health Organization }}

File:Monkeypox virus transmission.jpg

Monkeypox virus can be transmitted from one person to another through contact with infectious lesion material or fluid on the skin, in the mouth or on the genitals; this includes touching, close contact and during sex. It may also spread by means of respiratory droplets from talking, coughing or sneezing.{{Cite web |date=2 February 2023 |title=Mpox - How It Spreads |url=https://www.cdc.gov/poxvirus/mpox/if-sick/transmission.html |url-status=live |archive-url=https://web.archive.org/web/20230521160406/https://www.cdc.gov/poxvirus/mpox/if-sick/transmission.html |archive-date=21 May 2023 |access-date=23 May 2023 |website=Centers for Disease Control and Prevention}} During the 2022-2023 outbreak, transmission between people was almost exclusively via sexual contact.{{Cite web |date=28 April 2023 |title=Safer Sex, Social Gatherings, and Mpox |url=https://www.cdc.gov/poxvirus/mpox/prevention/sexual-health.html |url-status=live |archive-url=https://web.archive.org/web/20230529200408/https://www.cdc.gov/poxvirus/mpox/prevention/sexual-health.html |archive-date=29 May 2023 |access-date=26 May 2023 |website=Centers for Disease Control and Prevention}} There is a lower risk of infection from fomites (objects which can become infectious after being touched by an infected person) such as clothing or bedding, but precautions should be taken.

The virus then enters the body through broken skin, or mucosal surfaces such as the mouth, respiratory tract, or genitals.{{cite web |date=18 April 2023 |title=WHO Factsheet{{snd}}Mpox (Monkeypox) |url=https://www.who.int/news-room/fact-sheets/detail/monkeypox |url-status=live |archive-url=https://web.archive.org/web/20220421083742/https://www.who.int/news-room/fact-sheets/detail/monkeypox |archive-date=21 April 2022 |access-date=21 May 2023 |publisher=World Health Organization (WHO)}}{{Cite web |date=2022-08-30 |title=Brazil: Domestic puppy in Minas Gerais contracts monkeypox, Lived with confirmed human case |url=http://outbreaknewstoday.com/brazil-domestic-puppy-in-minas-gerais-contracts-monkeypox-lived-with-confirmed-human-case-31948/ |access-date=2023-06-10 |website=Outbreak News Today}}

There are two recorded instances of human to animal transmission. Both occurred during the 2022–2023 global mpox outbreak. In both cases, the owners of a pet dog first became infected with mpox and transmitted the infection to the pet.{{Cite journal |last1=Seang |first1=Sophie |last2=Burrel |first2=Sonia |last3=Todesco |first3=Eve |last4=Leducq |first4=Valentin |last5=Monsel |first5=Gentiane |last6=Le Pluart |first6=Diane |last7=Cordevant |first7=Christophe |last8=Pourcher |first8=Valérie |last9=Palich |first9=Romain |date=August 2022 |title=Evidence of human-to-dog transmission of monkeypox virus |url=https://doi.org/10.1016/S0140-6736(22)01487-8 |journal=The Lancet |volume=400 |issue=10353 |pages=658–659 |doi=10.1016/s0140-6736(22)01487-8 |issn=0140-6736 |pmc=9536767 |pmid=35963267}}

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Pox viruses have mechanisms to evade the hosts' innate and adaptive immune systems. Viral proteins, expressed by infected cells, employ multiple approaches to limit immune system activity, including binding to, and preventing activation of proteins within the host's immune system, and preventing infected cells from dying to enable them to continue replicating the monkey pox virus.{{Cite journal |last1=Lum |first1=Fok-Moon |last2=Torres-Ruesta |first2=Anthony |last3=Tay |first3=Matthew Z. |last4=Lin |first4=Raymond T. P. |last5=Lye |first5=David C. |last6=Rénia |first6=Laurent |last7=Ng |first7=Lisa F. P. |date=September 2022 |title=Monkeypox: disease epidemiology, host immunity and clinical interventions |journal=Nature Reviews Immunology |volume=22 |issue=10 |pages=597–613 |doi=10.1038/s41577-022-00775-4 |pmid=36064780 |pmc=9443635 |issn=1474-1741}}

The virus is subclassified into two clades, clade{{nbsp}}I and clade{{nbsp}}II. At the protein level, the clades share 170 orthologs, and their transcriptional regulatory sequences show no significant differences. 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.

Historically, the case fatality rate (CFR) of past outbreaks was estimated at between 1% and 10%, with clade I considered to be more severe than clade II.{{Cite journal |last=Vogel |first=Lauren |date=2022-08-15 |title=Making sense of monkeypox death rates |url=https://www.cmaj.ca/content/194/31/E1097 |url-status=live |journal=CMAJ |volume=194 |issue=31 |pages=E1097 |doi=10.1503/cmaj.1096012 |issn=0820-3946 |pmid=35970550 |pmc=9377567 |archive-url=https://web.archive.org/web/20230531173637/https://www.cmaj.ca/content/194/31/E1097 |archive-date=31 May 2023 |access-date=31 May 2023}} The CFR of the 2022-2023 global outbreak (caused by clade IIb) has been very low - estimated at 0.16%, with the majority of deaths in individuals who were already immunocompromised.{{Cite web |title=Mpox (monkeypox) - Prognosis |url=https://bestpractice.bmj.com/topics/en-gb/1611/prognosis |url-status=live |archive-url=https://web.archive.org/web/20230531173630/https://bestpractice.bmj.com/topics/en-gb/1611/prognosis |archive-date=31 May 2023 |access-date=2023-05-31 |website=BMJ Best Practice}}

File:Monkeypox By Country.svg

Monkeypox virus was first identified by Preben von Magnus in Copenhagen, Denmark, in 1958 in crab-eating macaque monkeys (Macaca fascicularis) being used as laboratory animals.{{cite journal | title = Monkeypox | journal = New Scientist | url = https://books.google.com/books?id=pO-YdZjojHEC&pg=PA682 | volume = 80 | date = 30 November 1978 | publisher = Reed Business Information | pages = 682– | issn = 0262-4079 | access-date = 3 November 2016 | archive-date = 13 January 2023 | archive-url = https://web.archive.org/web/20230113014032/https://books.google.com/books?id=pO-YdZjojHEC&pg=PA682 | url-status = live }} The virus was originally given the name monkeypox virus because it had been isolated from monkeys; subsequent research reveals that monkeys are not the main host. Other small mammals in the tropical forests of Central and West Africa{{cite journal |vauthors=Igiebor FA, Agbontaen OJ, Egharevba PA, Amengialue OO, Ehiaghe JI, Ovwero E, Ehiaghe FA |date=May 2022 |title=Monkeypox: Emerging and Re-Emerging Threats in Nigeria |url=https://scholar.google.com/citations?view_op=view_citation&hl=en&user=VjFa7yoAAAAJ&sortby=pubdate&authuser=1&citation_for_view=VjFa7yoAAAAJ:roLk4NBRz8UC |url-status=live |journal=Journal of Basic and Applied Sciences |location=Benin City, Nigeria |publisher=Faculty of Science, Benson Idahosa University |volume=7 |issue=1 |pages=119–132 |archive-url=https://web.archive.org/web/20220607134452/https://scholar.google.com/citations?view_op=view_citation&hl=en&user=VjFa7yoAAAAJ&sortby=pubdate&authuser=1&citation_for_view=VjFa7yoAAAAJ:roLk4NBRz8UC |archive-date=2022-06-07 |access-date=2022-06-07}} are suspected to form a natural reservoir.

The first human infection was diagnosed 1970, in the Democratic Republic of Congo. Small viral outbreaks with secondary human-to-human infection occur routinely in endemic areas of Central Africa; the primary route of infection is thought to be contact with the infected animals or their bodily fluids.{{cite journal |vauthors=Meyer H, Perrichot M, Stemmler M, Emmerich P, Schmitz H, Varaine F, Shungu R, Tshioko F, Formenty P |date=August 2002 |title=Outbreaks of disease suspected of being due to human monkeypox virus infection in the Democratic Republic of Congo in 2001 |journal=Journal of Clinical Microbiology |volume=40 |issue=8 |pages=2919–2921 |doi=10.1128/JCM.40.8.2919-2921.2002 |pmc=120683 |pmid=12149352}} The first reported outbreak in humans outside of Africa occurred in 2003 in the United States; it was traced to Gambian pouched rats which had been imported as exotic pets.{{cite web |date=11 May 2015 |title=2003 U.S. Outbreak Monkeypox |url=https://www.cdc.gov/poxvirus/monkeypox/outbreak.html |url-status=live |archive-url=https://web.archive.org/web/20171015202731/https://www.cdc.gov/poxvirus/monkeypox/outbreak.html |archive-date=15 October 2017 |access-date=15 October 2017 |website=U.S. Centers for Disease Control and Prevention (CDC) }} There have subsequently been a number of outbreaks to regions outside of the endemic areas in Central Africa, and 2 public health emergencies of international concern, the 2022–2023 mpox outbreak and the 2023–2024 mpox epidemic. In August 2024 it was reported that the UAE will donate Monkeypox vaccines to the Democratic Republic of Congo, Nigeria, South Africa, Ivory Coast, and Cameroon.{{Cite web |date=2024-08-31 |title=UAE donates monkeypox vaccines to 5 African countries |url=https://gulfnews.com/uae/health/uae-donates-monkeypox-vaccines-to-5-african-countries-1.103976464 |access-date=2024-09-22 |website=gulfnews.com |language=en}}

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{{Reflist}}

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• {{commonscat-inline}}
• [https://www.cdc.gov/ncidod/monkeypox/qa.htm CDC Questions and Answers About Monkeypox]
• [http://wonder.cdc.gov/wonder/prevguid/m0048673/m0048673.asp CDC – Human Monkeypox – Kasai Oriental, Zaire, 1996–1997] {{Webarchive|url=https://web.archive.org/web/20220523133526/https://wonder.cdc.gov/wonder/prevguid/m0048673/m0048673.asp |date=2022-05-23 }}
• [https://www.cdc.gov/ncidod/eid/vol7no3/hutin.htm CDC – Outbreak of Human Monkeypox, Democratic Republic of Congo, 1996 to 1997]
• [https://www.cdc.gov/ncidod/monkeypox/report060903.htm CDC Preliminary Report: Multistate Outbreak of Monkeypox in Persons Exposed to Pet Prairie Dogs]
• [https://www.nlm.nih.gov/cgi/mesh/2002/MB_cgi?term=MONKEYPOX+VIRUS National Library of Medicine – Monkeypox virus]
• [http://www.virology.net/Big_Virology/BVDNApox.html Virology.net Picturebook: Monkeypox] {{Webarchive|url=https://web.archive.org/web/20051028204824/http://www.virology.net/Big_Virology/BVDNApox.html |date=2005-10-28 }}
• [http://www.expasy.org/viralzone/all_by_species/149.html Viralzone: Orthopoxvirus]
• [http://www.viprbrc.org/brc/home.do?decorator=pox Virus Pathogen Database and Analysis Resource (ViPR): Poxviridae]
• [https://time.com/6187445/monkeypox-who-rename-stigma/ World Health Organization to rename the Monkeypox Virus]

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