Monkeypox virus

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Orthopoxvirus monkeypox
Monkeypox Virus (52103767506).jpg
Colorized transmission electron micrograph of monkeypox virus particles (teal) found within an infected cell (brown), cultured in the laboratory.
Virus classification OOjs UI icon edit-ltr.svg
(unranked): Virus
Realm: Varidnaviria
Kingdom: Bamfordvirae
Phylum: Nucleocytoviricota
Class: Pokkesviricetes
Order: Chitovirales
Family: Poxviridae
Genus: Orthopoxvirus
Species:
Orthopoxvirus monkeypox
Clades
  • Clade I
    • Clade Ia
    • Clade Ib
  • Clade II
    • Clade IIa
    • Clade IIb
Synonyms

MPV, MPXV, hMPXV

The monkeypox virus (MPV, MPXV, or hMPXV) [1] [lower-alpha 1] is a species of double-stranded DNA virus that causes mpox disease in humans and other mammals. It is a zoonotic virus belonging to the Orthopoxvirus genus, making it closely related to the variola, cowpox, and vaccinia viruses. MPV is oval, with a lipoprotein outer membrane. The genome is approximately 190 kb. Smallpox and monkeypox viruses are both orthopoxviruses, and the smallpox vaccine is effective against mpox if given within 3–5 years before the disease is contracted. [4] Symptoms of mpox in humans include a rash that forms blisters and then crusts over, fever, and swollen lymph nodes. [5] The virus is transmissible between animals and humans by direct contact to the lesions or bodily fluids. [6] The virus was given the name monkeypox virus after being isolated from monkeys, but most of the carriers of this virus are smaller mammals. [5]

Contents

The virus is endemic in Central Africa, where infections in humans are relatively frequent. [5] [7] Though there are many natural hosts for the monkeypox virus, the exact reservoirs and how the virus is circulated in nature needs to be studied further. [8]

Virology

Classification

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). [9] 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. [10] Members of the poxvirus family, include the monkeypox virus itself have been listed by the WHO as diseases with epidemic or pandemic potential. [11] 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. [11] [12] [13]

There are two subtypes or clades, clade I historically associated with the Congo Basin and clade II historically associated with West Africa. A global outbreak during 2022–2023 was caused by clade II. [5]

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. [14] Through phylogenetic analysis, it was found that MPV is not a direct descendant of the variola virus. [14]

Structure and genome

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

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. [15] 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. [16]

The genome of the monkeypox virus comprises 200 kb of double-stranded DNA coding for 191 proteins. [17] [18] 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. [19] 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. [16]

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. [16] To evade host immune systems, and buy more time for replication, monkeypox and other orthopox viruses have evolved mechanisms to evade host immune cells. [20]

Monkeypox virus size and structure in comparison to HIV, SARS-COV-2 and Poliovirus. Membranes and membrane-bound proteins are in purple, capsids are in dark blue, and genomes and nucleoid-associated proteins are in turquoise. Monkeypox viruses scale.png
Monkeypox virus size and structure in comparison to HIV, SARS-COV-2 and Poliovirus. Membranes and membrane-bound proteins are in purple, capsids are in dark blue, and genomes and nucleoid-associated proteins are in turquoise.

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. [21] [22] The factories are also where DNA replication, gene expression, and assembly of mature virions (MV) are located. [23]

MPV virions (MVs) are able to bind to the cell surface with the help of viral proteins. [24] Virus entry into the host cell plasma membrane is dependent on a neutral pH, otherwise entry occurs via a low-pH dependent endocytic route. [24] The MV of the monkeypox virus has an Entry Fusion Complex (EFC), allowing it to enter the host cell after attachment. [24]

The viral mRNA is translated into structural virion protein by the host ribosomes. [21] Gene expression begins when MPV releases viral proteins and enzymatic factors that disable the cell. [25] Mature virions are infectious. However, they will stay inside the cell until they are transported from the factories to the Golgi/endosomal compartment. [23] 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). [25] [21] [23] The VPS52 and VPS54 genes of the GARP complex, which is important for transport, are necessary for wrapping the virus, and formation of EVs. [23] DNA concatemers process the genomes, which appear in new virions, along with other enzymes, and genetic information needed for the replication cycle to occur. [25] EVs are necessary for the spread of the virus from cell-to-cell and its long-distance spread. [23]

Transmission

Animal to human

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. [26]

Human to human

Transmission scheme of the monkeypox virus Monkeypox virus transmission.jpg
Transmission scheme of the monkeypox virus

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. [5] [28] During the 2022-2023 outbreak, transmission between people was almost exclusively via sexual contact. [29] 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. [5]

The virus then enters the body through broken skin, or mucosal surfaces such as the mouth, respiratory tract, or genitals. [30] [31]

Human to animal

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. [32] [31]

Mpox disease

Human

This section is an excerpt from Mpox § Signs and symptoms.[ edit ]

Initial symptoms of mpox infection are fever, muscle pains, and sore throat, followed by an itchy or painful rash, headache, swollen lymph nodes, and fatigue. Not everyone will exhibit the complete range of symptoms. [33] [34]

Mpox patients usually become symptomatic about a week after infection. However the incubation period can vary in a range between one day and four weeks. [35] [36]

Animal

This section is an excerpt from Mpox § In other animals.[ edit ]
It is thought that small mammals provide a reservoir for the virus in endemic areas. [37] Spread among animals occurs via the fecal–oral route and through the nose, through wounds and eating infected meat. [38] The disease has also been reported in a wide range of other animals, including monkeys, anteaters, hedgehogs, prairie dogs, squirrels, and shrews. Signs and symptoms in animals are not well researched and further studies are in progress. [37]

Prevention

This section is an excerpt from Mpox § Prevention.[ edit ]

Vaccine

Historically, smallpox vaccine had been reported to reduce the risk of mpox among previously vaccinated persons in Africa. The decrease in immunity to poxviruses in exposed populations is a factor in the increasing prevalence of human mpox. It is attributed to waning cross-protective immunity among those vaccinated before 1980, when mass smallpox vaccinations were discontinued, and to the gradually increasing proportion of unvaccinated individuals. [39]

As of August 2024, there are four vaccines in use to prevent mpox, although supplies are limited. All were originally developed to combat smallpox. [40]

  • MVA-BN (marketed as Jynneos, Imvamune or Imvanex) manufactured by Bavarian Nordic. Licensed for use against mpox in Europe, United States and Canada. [41]
  • LC16 from KMB Biologics (Japan) – licensed for use in Japan. [42]
  • OrthopoxVac, licensed for use in Russia and manufactured by the State Research Center of Virology and Biotechnology VECTOR in Russia [43]
  • ACAM2000, manufactured by Emergent BioSolutions. Approved for use against mpox in the United States as of August 2024. [44] [45]

The MVA-BN vaccine, originally developed for smallpox, has been approved in the United States for use by persons who are either considered at high risk of exposure to mpox, or who may have recently been exposed to it. [46] [47] [48] [49] The United States Centers for Disease Control and Prevention (CDC) recommends that persons investigating mpox outbreaks, those caring for infected individuals or animals, and those exposed by close or intimate contact with infected individuals or animals should receive a vaccination. [50]

Other measures

The CDC has made detailed recommendations in addition to the standard precautions for infection control. These include that healthcare providers don a gown, mask, goggles, and a disposable filtering respirator (such as an N95), and that an infected person should be isolated a private room to keep others from possible contact. [51]

Those living in countries where mpox is endemic should avoid contact with sick mammals such as rodents, marsupials, non-human primates (dead or alive) that could harbour Orthopoxvirus monkeypox and should refrain from eating or handling wild game (bush meat). [52] [53]

During the 2022–2023 outbreak, several public health authorities launched public awareness campaigns in order to reduce spread of the disease. [54] [55] [56]

Treatment

This section is an excerpt from Mpox § Treatment.[ edit ]
Most cases of mpox present with mild symptoms and there is complete recovery within 2 to 4 weeks. [57] [53] There is no specific treatment for the disease, although antivirals such as tecovirimat have been approved for the treatment of severe mpox. [58] [59] [60] A 2023 Cochrane review found no completed randomised controlled trials studying therapeutics for the treatment of mpox. [61] The review identified non-randomised controlled trials which evaluated the safety of therapeutics for mpox, finding no significant risks from tecovirimat and low certainty evidence that suggests brincidofovir may cause mild liver injury. [61] Pain is common and may be severe; supportive care such as pain or fever control may be administered. [53] [62] Patients with mild disease should isolate at home, stay hydrated, eat well, and take steps to maintain their mental health. [33]

Immune system interaction

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. [63]

Variants and clades

The virus is subclassified into two clades, clade I and clade II. [5] At the protein level, the clades share 170 orthologs, and their transcriptional regulatory sequences show no significant differences. [11] 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. [11]

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. [64] 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. [65]

Clades and subclades of Orthopoxvirus monkeypox
Name [66] Former names [66] Nations [67] [68]
Clade IClade IaCongo Basin

Central African

Clade Ib
Clade IIClade IIaWest African
Clade IIbWidespread globally - See 2022–2023 mpox outbreak § Cases per country and territory

History

A map of the spread of the monkeypox virus globally. .mw-parser-output .legend{page-break-inside:avoid;break-inside:avoid-column}.mw-parser-output .legend-color{display:inline-block;min-width:1.25em;height:1.25em;line-height:1.25;margin:1px 0;text-align:center;border:1px solid black;background-color:transparent;color:black}.mw-parser-output .legend-text{} Endemic clade II Endemic clade I Both clades recorded Clade IIb outbreak in 2022-2023 Monkeypox By Country.svg
A map of the spread of the monkeypox virus globally.
  Endemic clade II
  Endemic clade I
  Both clades recorded
  Clade IIb outbreak in 2022–2023

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. [69] 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 [70] are suspected to form a natural reservoir. [11]

The first human infection was diagnosed 1970, in the Democratic Republic of Congo. [5] 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. [71] 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. [72] 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. [73]

Notes

  1. ↑ The World Health Organization (the authority on disease names) announced the new name "mpox" in November 2022. But virus naming is the responsibility of the International Committee on the Taxonomy of Viruses (ICTV), which is currently reviewing all orthopoxvirus species. In June 2024, the official species name of the virus was updated to Orthopoxvirus monkeypox as part of this update. [2] [3]

Related Research Articles

<span class="mw-page-title-main">Mpox</span> Viral disease of humans and animals

Mpox is an infectious viral disease that can occur in humans and other animals. Symptoms include a rash that forms blisters and then crusts over, fever, and swollen lymph nodes. The illness is usually mild, and most infected individuals recover within a few weeks without treatment. The time from exposure to the onset of symptoms ranges from three to seventeen days, and symptoms typically last from two to four weeks. However, cases may be severe, especially in children, pregnant women, or people with suppressed immune systems.

<span class="mw-page-title-main">Vaccinia</span> Strain of poxvirus

The vaccinia virus is a large, complex, enveloped virus belonging to the poxvirus family. It has a linear, double-stranded DNA genome approximately 190 kbp in length, which encodes approximately 250 genes. The dimensions of the virion are roughly 360 × 270 × 250 nm, with a mass of approximately 5–10 fg. The vaccinia virus is the source of the modern smallpox vaccine, which the World Health Organization (WHO) used to eradicate smallpox in a global vaccination campaign in 1958–1977. Although smallpox no longer exists in the wild, vaccinia virus is still studied widely by scientists as a tool for gene therapy and genetic engineering.

Modified vaccinia Ankara (MVA) is an attenuated (weakened) strain of the vaccinia virus. It is being used as a vaccine against smallpox and mpox, having fewer side effects than smallpox vaccines derived from other poxviruses.

Orthopoxvirus is a genus of viruses in the family Poxviridae and subfamily Chordopoxvirinae. Vertebrates, including mammals and humans, and arthropods serve as natural hosts. There are 12 species in this genus. Diseases associated with this genus include smallpox, cowpox, horsepox, camelpox, and mpox. The most widely known member of the genus is Variola virus, which causes smallpox. It was eradicated globally by 1977, through the use of Vaccinia virus as a vaccine. The most recently described species is the Alaskapox virus, first isolated in 2015.

<span class="mw-page-title-main">Tecovirimat</span> Antiviral medication

Tecovirimat, sold under the brand name Tpoxx among others, is an antiviral medication with activity against orthopoxviruses such as smallpox and mpox. In 2018 it became the first antipoxviral drug approved in the United States.

<span class="mw-page-title-main">2003 Midwest monkeypox outbreak</span> Outbreak of monkeypox in the United States

An outbreak of human monkeypox began in May 2003 in the United States. By July, a total of 71 cases were found in six Midwestern states including Wisconsin, Indiana (16), Illinois (12), Kansas (1), Missouri (2), and Ohio (1). The cause of the outbreak was traced to three species of African rodents imported from Ghana on April 9, 2003, into the United States by an exotic animal importer in Texas. These were shipped from Texas to an Illinois distributor, who housed them with prairie dogs, which then became infected.

<span class="mw-page-title-main">2022–2023 mpox outbreak</span> World public health emergency (May 2022 – May 2023)

In May 2022, the World Health Organization (WHO) made an emergency announcement of the existence of a multi-country outbreak of mpox, a viral disease then commonly known as "monkeypox". The initial cluster of cases was found in the United Kingdom, where the first case was detected in London on 6 May 2022 in a patient with a recent travel history from Nigeria where the disease has been endemic. On 16 May, the UK Health Security Agency (UKHSA) confirmed four new cases with no link to travel to a country where mpox is endemic. Subsequently, cases have been reported from many countries and regions. The outbreak marked the first time mpox had spread widely outside Central and West Africa. The disease had been circulating and evolving in human hosts over several years before the outbreak and was caused by the clade IIb variant of the virus.

<span class="mw-page-title-main">2022–2023 mpox outbreak in the United Kingdom</span> Ongoing viral outbreak

The 2022–2023 mpox outbreak in the United Kingdom is part of the larger outbreak of human mpox caused by the West African clade (type) of the monkeypox virus. The United Kingdom was the first country, outside of the endemic African areas, to experience an outbreak. As of 22 July 2022, there were 2,208 confirmed cases in the United Kingdom, with 2,115 in England, 54 in Scotland, 24 in Wales, and 15 in Northern Ireland.

<span class="mw-page-title-main">2022–2023 mpox outbreak in the United States</span> Ongoing viral outbreak

The 2022–2023 mpox outbreak in the United States was part of the larger outbreak of human mpox caused by the West African clade of the monkeypox virus. The United States was the fourth country outside of the African countries with endemic mpox to experience an outbreak in 2022. The first case was documented in Boston, Massachusetts, on May 17, 2022. As of August 2022, mpox had spread to all 50 states in the United States, as well as Washington, D.C., and Puerto Rico. The United States had the highest number of mpox cases in the world during the outbreak. California had the highest number of mpox cases in the United States.

The 2022–2023 mpox outbreak in Portugal is part of the larger outbreak of human mpox caused by the West African clade of the monkeypox virus. Portugal was the third country, outside of the African countries with endemic mpox, to experience an outbreak in 2022.

The 2022–2023 mpox outbreak in Italy is part of the larger outbreak of human mpox caused by the West African clade of the monkeypox virus. Italy was the sixth country, outside of the African countries with endemic mpox, to experience an outbreak in 2022. The first case was documented in Rome, Italy, on May 19, 2022. As of August 5th, Italy has 505 cases.

The 2022–2023 mpox outbreak in Belgium is part of the larger outbreak of human mpox caused by the West African clade of the monkeypox virus. Belgium was the fifth country, outside of the African countries with endemic mpox, to experience an outbreak in 2022. The first case was documented in Antwerp, Belgium, on 19 May 2022. As of 10 August, Belgium has 546 cases and 1 suspected case.

The 2022–2023 mpox outbreak in Israel is a part of the ongoing outbreak of human mpox caused by the West African clade of the monkeypox virus. The outbreak was first reported in Israel on 20 May 2022 when the Health Ministry announced a suspected case which was confirmed on 21 May 2022. One month later, on 21 June, the first locally transmitted case was reported.

The 2022–2023 mpox outbreak in Switzerland is a part of the outbreak of human mpox caused by the West African clade of the monkeypox virus. The outbreak started in Switzerland on 19 May 2022, with the country since then becoming one of the most affected in Europe.

The 2022–2023 mpox outbreak in Austria is part of the larger outbreak of human mpox caused by the West African clade of the monkeypox virus. Austria is the fifteenth country outside of Africa to experience an endemic mpox outbreak. The first case was reported in Vienna, Austria, on 22 May 2022. As of 2 December, Austria has confirmed a total of 327 cases.

<span class="mw-page-title-main">2022–2023 mpox outbreak in Mexico</span> Ongoing viral outbreak

The 2022–2023 mpox outbreak in Mexico is part of the larger outbreak of human mpox caused by the West African clade of the monkeypox virus. Mexico is the twenty-fourth country outside of Africa to experience an endemic mpox outbreak. The first case was reported in Mexico City, Mexico, on May 28, 2022. As of December 8th 2022, Mexico had confirmed a total of 3455 cases in all 32 states and 4 deaths.

<span class="mw-page-title-main">2022–2023 mpox outbreak in Brazil</span> Ongoing outbreak of mpox in Brazil

The 2022–2023 mpox outbreak in Brazil is a part of the ongoing outbreak of human mpox caused by the West African clade of the monkeypox virus. The outbreak was first reported in Brazil on 9 June 2022 when a man in São Paulo was registered as the country's index case.

The 2022–2023 mpox outbreak in the Netherlands is an ongoing global outbreak which has also spread in the Netherlands. The RIVM declared the disease an A-disease which makes it mandatory to report suspected cases to the GGD. The first human case of mpox in the Netherlands has been identified at the 21 May 2022. The outbreak does have a noticeable impact at the society, especially with people spreading misinformation related to the virus. The ongoing COVID-19 pandemic in the Netherlands has increased the fear among the community for a new pandemic like mpox.

The 2022–2023 mpox outbreak in Singapore is a part of the global outbreak of human mpox caused by the West African clade of the monkeypox virus. According to the Ministry of Health (MOH), Singapore's first imported mpox case was reported on 20 June 2022. It was the first ever confirmed case in Southeast Asia.

The 2022-2023 mpox outbreak in the Republic of Ireland is part of the larger ongoing global outbreak of human mpox caused by Clade II of the monkeypox virus. The first case in the Republic was confirmed on 27 May 2022.

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