The monkeypox virus (MPV, MPXV, or hMPXV) is a species of
double-stranded DNA viruses
A DNA virus is a virus that has a genome made of deoxyribonucleic acid (DNA) that is replicated by a DNA polymerase. They can be divided between those that have two strands of DNA in their genome, called double-stranded DNA (dsDNA) viruses, and t ...
that cause
mpox disease in humans and other mammals. It is a
zoonotic
A zoonosis (; plural zoonoses) or zoonotic disease is an infectious disease of humans caused by a pathogen (an infectious agent, such as a virus, bacterium, parasite, fungi, or prion) that can jump from a non-human vertebrate to a human. When h ...
virus belonging to the ''
Orthopoxvirus
''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 wi ...
'' genus, making it closely related to the
variola
Smallpox was an infectious disease caused by Variola virus (often called Smallpox virus), which belongs to the genus '' Orthopoxvirus''. The last naturally occurring case was diagnosed in October 1977, and the World Health Organization (WH ...
,
cowpox
Cowpox is an infectious disease caused by 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 ...
, and
vaccinia
The vaccinia virus (VACV or VV) 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 ...
viruses. MPV is oval, with a lipoprotein outer membrane. Its genome is approximately 190 kb.
Smallpox
Smallpox was an infectious disease caused by Variola virus (often called Smallpox virus), which belongs to the genus '' Orthopoxvirus''. The last naturally occurring case was diagnosed in October 1977, and the World Health Organization (W ...
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. Symptoms of mpox in humans include a
rash
A rash is a change of the skin that affects its color, appearance, or texture.
A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracke ...
that forms
blister
A blister is a small pocket of body fluid (lymph, serum, plasma, blood, or pus) within the upper layers of the skin, usually caused by forceful rubbing (friction), burning, freezing, chemical exposure or infection. Most blisters are filled ...
s and then crusts over, fever, and
swollen lymph nodes.
The virus is transmissible between animals and humans by direct contact to the lesions or via bodily fluids.
The virus was given the name monkeypox virus after being isolated from monkeys, but most of the carriers of this virus are smaller mammals.
The virus is endemic in
Central Africa
Central Africa (French language, French: ''Afrique centrale''; Spanish language, Spanish: ''África central''; Portuguese language, Portuguese: ''África Central'') is a subregion of the African continent comprising various countries accordin ...
, where infections in humans are relatively frequent.
Though there are many natural hosts for the monkeypox virus, the exact
reservoirs
A reservoir (; ) is an enlarged lake behind a dam, usually built to store fresh water, often doubling for hydroelectric power generation.
Reservoirs are created by controlling a watercourse that drains an existing body of water, interrup ...
and how the virus is circulated in nature needs to be studied further.
Virology
Classification
The monkeypox virus is a
zoonotic
A zoonosis (; plural zoonoses) or zoonotic disease is an infectious disease of humans caused by a pathogen (an infectious agent, such as a virus, bacterium, parasite, fungi, or prion) that can jump from a non-human vertebrate to a human. When h ...
virus belonging to the genus ''
Orthopoxvirus
''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 wi ...
,'' which itself is a member of the family ''
Poxviridae
''Poxviridae'' is a family of double-stranded DNA viruses. Vertebrates and arthropods serve as natural hosts. The family contains 22 genera that are assigned to two subfamilies: ''Chordopoxvirinae'' and ''Entomopoxvirinae''. ''Entomopoxvirinae'' ...
'' (also known as the poxvirus family). Of note, the ''Orthopoxvirus'' genus includes the
''variola virus'' that prior to
eradication via the advent of the
smallpox vaccine
The smallpox vaccine is used to prevent smallpox infection caused by the variola virus. It is the first vaccine to have been developed against a contagious disease. In 1796, British physician Edward Jenner demonstrated that an infection with th ...
, was the cause of the infectious human disease known as
smallpox
Smallpox was an infectious disease caused by Variola virus (often called Smallpox virus), which belongs to the genus '' Orthopoxvirus''. The last naturally occurring case was diagnosed in October 1977, and the World Health Organization (W ...
.
Members of the poxvirus family, include the ''monkeypox virus'' itself have been listed by the WHO as diseases with epidemic or pandemic potential.
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.
There are two subtypes or
clade
In biology, a clade (), also known as a Monophyly, monophyletic group or natural group, is a group of organisms that is composed of a common ancestor and all of its descendants. Clades are the fundamental unit of cladistics, a modern approach t ...
s, cladeI historically associated with the
Congo Basin
The Congo Basin () is the sedimentary basin of the Congo River. The Congo Basin is located in Central Africa, in a region known as west equatorial Africa. The Congo Basin region is sometimes known simply as the Congo. It contains some of the larg ...
and cladeII historically associated with
West Africa
West Africa, also known as Western Africa, is the westernmost region of Africa. The United Nations geoscheme for Africa#Western Africa, United Nations defines Western Africa as the 16 countries of Benin, Burkina Faso, Cape Verde, The Gambia, Gha ...
. 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.
Through phylogenetic analysis, it was found that MPV is not a direct descendant of the variola virus.
Structure and genome
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. Typical DNA viruses replicate and express their genome in the nucleus of
eukaryotic
The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...
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.
The genome of the monkeypox virus comprises 200
kb of double-stranded DNA coding for 191 proteins.
Similar to other poxviruses, the
virions
A virion (plural, ''viria'' or ''virions'') is an inert virus particle capable of invading a cell. Upon entering the cell, the virion disassembles and the genetic material from the virus takes control of the cell infrastructure, thus enabling th ...
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. 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.
Replication and life cycle
As an ''Orthopoxvirus'', MPV replication occurs entirely in the cell
cytoplasm
The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell a ...
within 'factories' – created from the host rough
endoplasmic reticulum
The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...
(ER) – where viral mRNA transcription and translation also take place.
The factories are also where DNA replication, gene expression, and assembly of mature virions (MV) are located.
MPV virions (MVs) are able to bind to the cell surface with the help of viral proteins.
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
ribosome
Ribosomes () are molecular machine, macromolecular machines, found within all cell (biology), cells, that perform Translation (biology), biological protein synthesis (messenger RNA translation). Ribosomes link amino acids together in the order s ...
s.
Gene expression begins when MPV releases viral proteins and enzymatic factors that disable the cell.
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.
Transmission
Animal to human
Zoonotic
A zoonosis (; plural zoonoses) or zoonotic disease is an infectious disease of humans caused by a pathogen (an infectious agent, such as a virus, bacterium, parasite, fungi, or prion) that can jump from a non-human vertebrate to a human. When h ...
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.
Human to human

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.
During the 2022-2023 outbreak, transmission between people was almost exclusively via sexual contact. There is a lower risk of infection from
fomite
A fomite () or fomes () is any inanimate object that, when contaminated with or exposed to infectious agents (such as pathogenic bacteria, viruses or fungi), can transfer disease to a new host.
Transfer of pathogens by fomites
A fomite is any ...
s (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.
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.
Mpox disease
Human
Animal
Prevention
Treatment
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.
Variants and clades
The virus is subclassified into two clades, cladeI and cladeII.
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
In epidemiology, case fatality rate (CFR) – or sometimes more accurately case-fatality risk – is the proportion of people who have been diagnosed with a certain disease and end up dying of it. Unlike a disease's mortality rate, the CFR does ...
(CFR) of past outbreaks was estimated at between 1% and 10%, with clade I considered to be more severe than clade II.
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
Immunodeficiency, also known as immunocompromise, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that affe ...
.
History

Monkeypox virus was first identified by
Preben von Magnus in
Copenhagen, Denmark, in 1958 in
crab-eating macaque
The crab-eating macaque (''Macaca fascicularis''), also known as the long-tailed macaque or cynomolgus macaque, is a cercopithecine primate native to Southeast Asia. As a synanthropic species, the crab-eating macaque thrives near human settlem ...
monkeys (''Macaca fascicularis'') being used as
laboratory animals.
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
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.
The first reported outbreak in humans outside of Africa occurred in
2003 in the United States; it was traced to
Gambian pouched rat
The Gambian pouched rat (''Cricetomys gambianus''), also Common name, commonly known as the African giant pouched rat, is a species of nocturnal pouched rat of the giant pouched rat genus ''Cricetomys'', in the Family (biology), family Nesomyidae ...
s which had been imported as exotic pets.
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
In public relations and communication science, publics are groups of individual people, and the public (a.k.a. the general public) is the totality of such groupings. This is a different concept to the sociological concept of the ''Öffentlich ...
, the
2022–2023 mpox outbreak
In May 2022, the World Health Organization (WHO) made an emergency announcement of the existence of a multi-country disease outbreak, outbreak of mpox, a viral disease then commonly known as "monkeypox". The initial cluster of cases was found i ...
and the
2023–2024 mpox epidemic. In August 2024 it was reported that the
UAE
The United Arab Emirates (UAE), or simply the Emirates, is a country in West Asia, in the Middle East, at the eastern end of the Arabian Peninsula. It is a federal elective monarchy made up of seven emirates, with Abu Dhabi serving as i ...
will donate Monkeypox vaccines to the Democratic Republic of Congo, Nigeria, South Africa, Ivory Coast, and Cameroon.
Notes
References
External links
*
CDC Questions and Answers About MonkeypoxCDC – Human Monkeypox – Kasai Oriental, Zaire, 1996–1997
*
ttps://www.cdc.gov/ncidod/monkeypox/report060903.htm CDC Preliminary Report: Multistate Outbreak of Monkeypox in Persons Exposed to Pet Prairie DogsNational Library of Medicine – Monkeypox virus
Virus Pathogen Database and Analysis Resource (ViPR): PoxviridaeWorld Health Organization to rename the Monkeypox Virus
{{Authority control
Animal viruses
Human viruses
Species described in 1958
Viruses described in the 20th century
Chordopoxvirinae
Mpox