Monkeypox virus

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Monkeypox virus
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:
Monkeypox virus
Clades
  • Clade I (Congo Basin)
  • Clade II (West African)
    • Clade IIa
    • Clade IIb
Synonyms

MPV, MPXV, hMPXV, [ongoing consideration about changing the virus's name]

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. The monkeypox virus is a zoonotic virus belonging to the orthopoxvirus genus, making it closely related to the variola, cowpox, and vaccinia viruses. MPV is oval-shaped with a lipoprotein outer membrane. The genome is approximately 190 kb.

The smallpox and monkeypox viruses are both orthopoxviruses, and the smallpox vaccine is effective against mpox if given within 3–5 years before contracting the disease. [3] Symptoms of mpox in humans include a rash that forms blisters and then crusts over, fever, and swollen lymph nodes. [4] The virus is transmissible between animals and humans by direct contact to the lesions or bodily fluids. [5] The virus was given the name monkeypox virus after being isolated from monkeys, but most of the carriers of this virus are small mammals. [4]

The virus is endemic in Central Africa, where infections in humans are relatively frequent. [4] [6] 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. [7]

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. [8] There are two subtypes, 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. [4]

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. [9] Through phylogenetic analysis, it was found that MPV is not a direct descendant of the variola virus. [9]

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. [10] Typical DNA viruses replicate and express their genome in the nucleus of eukaryotic cells, relying heavily on the host cell's machinery. However, the monkeypox viruses rely mostly on the protein encoded in their genome that allows them to replicate in the cytoplasm. [11]

The genome of the monkeypox virus comprises 200 kb of double stranded DNA coding for 191 proteins. [12] [13] Similar to other poxviruses, the virions of monkey pox have large oval shaped 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. [14] 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 towards interactions between the virus and the host cell such as spike protein characteristics. [11]

Monkeypox virus is relatively large compared to other viruses. This makes it harder for the virus to breach the host defenses, such as crossing past gap junctions. Furthermore, the large size makes it harder for the virus to quickly replicate and evade immune response. [11] To evade host immune systems, and buy more time for replication, the monkeypox and other orthopox viruses have evolved mechanisms to evade host immune cells. [15]

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.
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)

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. [16] [17] The factories are also where DNA replication, gene expression, and mature virions (MV) are created. [18]

MVs are able to bind to the cell surface with the help of viral proteins. [19] Virus entry into the host cell plasma membrane is dependent on a neutral pH, otherwise entry occurs via a low-pH dependent endocytic route. [19] The MV of the monkeypox virus has an Entry Fusion Complex (EFC), allowing it to enter the host cell after attachment. [19]

Translation of mRNA into structural virions occurs using the host ribosomes. [16] Gene expression begins when MPV releases viral proteins and enzymatic factors that disable the cell. [20] Mature virions are infectious, however, they will stay inside the cell, until they are transported from the factories to the Golgi/endosomal comportment. [18] Protein synthesis allows for the ER membrane of the factory to dismantle, while small two lipid bilayer membranes will appear to encapsulate the genomes of new virions, now extracellular viruses (EVs). [20] [16] [18] The VPS52 and VPS54 genes of the GARP complex, which is important for transport, are necessary for wrapping the virus, and formation of EVs. [18] DNA concatemers process the genomes, which appear in new virions, along with other enzymes, and genetic information needed for the replication cycle to occur. [20] EVs are necessary for the spread of the virus from cell-to-cell and its long-distance spread. [18]

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 evidence of 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. [21]

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. [4] [23] During the 2022-2023 outbreak, transmission between people was almost exclusively via sexual contact. [24] 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. [4]

The virus then enters the body through broken skin, or mucosal surfaces such as the mouth, respiratory tract, or genitals. [25] [26]

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. [27] [26]

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. [28] [29]

Most mpox patients become symptomatic 4–11 days after infection. However, the incubation period can be as short as 1 day. The 2022–2023 outbreak revealed that incubation periods of up to 4 weeks are possible, with 5% of cases having incubation periods longer than the previously assumed 21 days. [28] [30]

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. [31] Spread among animals occurs via the fecal–oral route and through the nose, through wounds and eating infected meat. [32] 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. [31]

Prevention

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

The MVA-BN vaccine, originally developed for smallpox, has been approved for use by persons who are either considered at high risk of exposure to mpox, or who may have recently been exposed to it. [33] [34] [35] 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. [36]

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. [37]

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. [38] There is no specific treatment for the disease, although antivirals such as tecovirimat have been approved for the treatment of severe mpox. [39] [40] [41] A 2023 Cochrane review found no completed randomised controlled trials studying therapeutics for the treatment of Mpox. [42] 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. [42] Pain is common and may be severe; supportive care such as pain or fever control may be administered. [38] [43] Patients with mild disease should isolate at home, stay hydrated, eat well, and take steps to maintain their mental health. [28]

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. [44]

Variants and clades

The virus is subclassified into two clades, Clade I and Clade II. [4] At the protein level, the clades share 170 orthologs, and their transcriptional regulatory sequences show no significant differences. [8] 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. [8]

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. [45] 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. [46]

Clades and subclades of Monkeypox virus
Name [47] Former names [47] Nations [48] [49]
Clade ICongo Basin

Central African

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. [50] 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. [51] are suspected to form a natural reservoir. [8]

The first human infection was diagnosed 1970, in the Democratic Republic of Congo. [4] 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. [52] 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. [53] There have subsequently been a number of outbreaks to regions outside of the endemic areas in Central Africa.

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. As of March 2023, the official name of the virus remains "monkeypox virus". [2]

Related Research Articles

<span class="mw-page-title-main">Cowpox</span> Disease of humans and animals

Cowpox is an infectious disease caused by the cowpox virus (CPXV). It presents with large blisters in the skin, a fever and swollen glands, historically typically following contact with an infected cow, though in the last several decades more often from infected cats. The hands and face are most frequently affected and the spots are generally very painful.

<i>Paramyxoviridae</i> Family of viruses

Paramyxoviridae is a family of negative-strand RNA viruses in the order Mononegavirales. Vertebrates serve as natural hosts. Diseases associated with this family include measles, mumps, and respiratory tract infections. The family has four subfamilies, 17 genera, three of which are unassigned to a subfamily, and 78 species.

<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 of those infected will recover within a few weeks without treatment. The time from exposure to onset of symptoms ranges from five to twenty-one days and symptoms typically last from two to four weeks. 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

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.

<i>Influenza A virus</i> Species of virus

Influenza A virus (IAV) is a pathogen that causes the flu in birds and some mammals, including humans. It is an RNA virus whose subtypes have been isolated from wild birds. Occasionally, it is transmitted from wild to domestic birds, and this may cause severe disease, outbreaks, or human influenza pandemics.

<i>Human metapneumovirus</i> Species of virus

Human metapneumovirus is a negative-sense single-stranded RNA virus of the family Pneumoviridae and is closely related to the Avian metapneumovirus (AMPV) subgroup C. It was isolated for the first time in 2001 in the Netherlands by using the RAP-PCR technique for identification of unknown viruses growing in cultured cells. As of 2016, it was the second most common cause of acute respiratory tract illness in otherwise-healthy children under the age of 5 in a large US outpatient clinic.

<i>Poxviridae</i> Family of viruses

Poxviridae is a family of double-stranded DNA viruses. Vertebrates and arthropods serve as natural hosts. There are currently 83 species in this family, divided among 22 genera, which are divided into two subfamilies. Diseases associated with this family include smallpox.

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.

<i>Andes orthohantavirus</i> Species of virus

Andes orthohantavirus (ANDV), a species of Orthohantavirus, is a major causative agent of hantavirus cardiopulmonary syndrome (HCPS) and hantavirus pulmonary syndrome (HPS) in South America. It is named for the Andes mountains of Chile and Argentina, where it was first discovered. Originating in the reservoir of rodents, Andes orthohantavirus is easily transmitted to humans who come into contact with infected rodents or their fecal droppings. However, infected rodents do not appear ill, so there is no readily apparent indicator to determine whether the rodent is infected or not. Additionally, Andes orthohantavirus, specifically, is the only hantavirus that can be spread by human to human contact via bodily fluids or long-term contact from one infected individual to a healthy person.

<i>Sindbis virus</i> Species of virus

Sindbis virus (SINV) is a member of the Togaviridae family, in the Alphavirus genus. The virus was first isolated in 1952 in Cairo, Egypt. The virus is transmitted by mosquitoes. SINV is linked to Pogosta disease (Finland), Ockelbo disease (Sweden) and Karelian fever (Russia). In humans, the symptoms include arthralgia, rash and malaise. Sindbis virus is widely and continuously found in insects and vertebrates in Eurasia, Africa, and Oceania. Clinical infection and disease in humans however has almost only been reported from Northern Europe, where SINV is endemic and where large outbreaks occur intermittently. Cases are occasionally reported in Australia, China, and South Africa.

<span class="mw-page-title-main">Virus</span> Infectious agent that replicates in cells

A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Viruses are found in almost every ecosystem on Earth and are the most numerous type of biological entity. Since Dmitri Ivanovsky's 1892 article describing a non-bacterial pathogen infecting tobacco plants and the discovery of the tobacco mosaic virus by Martinus Beijerinck in 1898, more than 11,000 of the millions of virus species have been described in detail. The study of viruses is known as virology, a subspeciality of microbiology.

<span class="mw-page-title-main">Marburg virus</span> Species of filamentous virus responsible for hemorrhagic fever

Marburg virus (MARV) is a hemorrhagic fever virus of the Filoviridae family of viruses and a member of the species Marburg marburgvirus, genus Marburgvirus. It causes Marburg virus disease in primates, a form of viral hemorrhagic fever. The virus is considered to be extremely dangerous. The World Health Organization (WHO) rates it as a Risk Group 4 Pathogen. In the United States, the National Institute of Allergy and Infectious Diseases ranks it as a Category A Priority Pathogen and the Centers for Disease Control and Prevention lists it as a Category A Bioterrorism Agent. It is also listed as a biological agent for export control by the Australia Group.

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

Beginning in May 2003, by July a total of 71 cases of human monkeypox 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.

Raccoonpox virus (RCN) is a double-stranded DNA virus and a member of the orthopoxviruses in the family Poxviridae and subfamily Chordopoxvirinae which consists of eight genera: Avipoxvirus, Capripoxvirus, Leporipoxvirus, Molluscipoxvirus, Orthopoxvirus, Parapoxvirus, Suipoxvirus and Yatapoxvirus Vertebrates are the natural host of Chordopoxvirinae subfamily viruses. More specifically, raccoons are the natural hosts of RCN. RCN was isolated in 1961 from the upper respiratory tissues of 2 raccoons in a group of 92 observably healthy raccoons trapped close to Aberdeen, Maryland.

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

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. 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. There is evidence that the disease had been circulating and evolving in human hosts over a number of years prior to the outbreak. The outbreak was of the Clade IIb variant of the virus.

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 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.

References

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