The monkeypox virus (MPV, MPXV, or hMPXV), also called the mpox virus,[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 (VARV), cowpox (CPX), and vaccinia (VACV) 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.[2] Symptoms of mpox in humans include a rash that forms blisters and then crusts over, fever, and swollen lymph nodes.[3] The virus is transmissible between animals and humans by direct contact to the lesions or bodily fluids.[4] The virus was given the name monkeypox virus after being isolated from monkeys, but most of the carriers of this virus are small mammals.[3]
Variation in virulence of the virus has been observed in isolates from Central Africa, where strains are more virulent than those from Western Africa.[5] The two areas have distinct clades of the virus, termed Clade I and Clade II.[3] 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.[6]
MPV is part of the genus Orthopoxvirus, belonging to the Poxviridae family, which have been listed by the WHO as diseases with epidemic or pandemic potential.[7] There are two major clades, Clade I associated mainly with the Congo Basin and Clade II associated with the West Africa. Clade I has been found to be more virulent.[8]
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 descendent of the variola virus.[9]
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]
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]
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 ranging from rope squirrels, tree squirrels, Gambian pouched rats, dormice, 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]
Mpox 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.[3][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.[3]
The virus then enters the body through broken skin, or mucosal surfaces such as the mouth, respiratory tract, or genitals.[25][26]
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]
The incubation period for mpox is between 3 and 17 days. 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]
The rash comprises many small lesions which may appear on the palms and soles, face, mouth and throat, genitals or anus.[28] They begin as small flat spots, before becoming small bumps which then fill with fluid and subsequently burst and scab over, persisting for around ten days.[29]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]Pox viruses have mechanisms to evade the hosts' innate and adaptive immune systems. When infected human fibroblast cells have been observed to show cytopathic changes, but gene expression of the host cell remains unchanged. Interferon produced by human fibroblast cells were not sufficient to slow viral replication.[43] The monkeypox virus gene BR-209 is an interleukin-1β (IL-1β) inhibitor that prevents interaction with the receptor.[44] The viral complement control protein (CCP), also known as MOPICE, a virulence factor, allows the virus to evade neutralization, opsonization, viral particle lysis, and phagocytosis.[45]
The monkey pox virus can prevent apoptosis in infected cells by targeting apoptotic pathways; the mechanism is still under research.[46][44] Moreover, the monkey pox virus can evade cytotoxicity mediated by t-cell and natural killer cells by producing MHC classI-like protein(OMCP) which resembles MHC class I module and it binds to NKG2D. Natural killer T cells continually survey cells with NKG2D for absence of MHC class I proteins; the monkeypox virus with its OMCP passes the check.[44] The virus also produces other proteins that further block cytotoxic activities. Evading the host immune system is crucial because of how large the monkeypox virus is.
In short, MPV has a unique immune system, MHC dependent, evasion tactic to evade antiviral CD4+ and CD8+ T cell responses.[47]
The virus is subclassified into two clades, Clade I and Clade II.[3] At the protein level, the clades share 170 orthologs, and their transcriptional regulatory sequences show no significant differences.[7] 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.[7]
The clades vary in virulence, with clade I having more human-human transmission, and having a higher mortality rate in non-vaccinated people.[7] The 2022–2023 mpox outbreak was caused by the clade II of the virus.[48]
Monkeypox virus is carried by various animals, including primates,[53] and causes disease in both primates and in other animals. It was first identified by Preben von Magnus in Copenhagen, Denmark, in 1958 in crab-eating macaque monkeys (Macaca fascicularis) being used as laboratory animals.[54] The virus was given the name monkeypox virus after being isolated from monkeys, but most of the carriers of this virus are rodents.
The virus is mainly found in the tropical forests of Central and West Africa.[55]
The virus was first discovered in humans in 1970. Between 1970 and 1986, over 400 cases in humans were reported. Small viral outbreaks with secondary human-to-human infection occur routinely in endemic areas.[56] The primary route of infection is thought to be contact with the infected animals or their bodily fluids.[56] The first reported outbreak outside Africa occurred in 2003 in the Midwestern United States in Illinois, Indiana, and Wisconsin, with one occurrence in New Jersey. The 2003 outbreak in the United States was traced to prairie dogs infected from an imported Gambian pouched rat from Ghana.[57] A significant outbreak in Nigeria occurred in 2017.[58]
The monkeypox virus is a highly complex virus and is not yet fully understood. Many laboratories across the globe continue to study the virus as it has been spreading significantly outside of its endemic areas. Pathologic examination of the virus are carefully being done on formalin-fixed or inactivated tissues. One study done by Manes et al. inoculated a MPV strain obtained from the CDC into HeLa cells. The original strain was obtained from a victim of the virus.[59] Most of our current understanding of the monkeypox virus stems from the knowledge cultivated from studying the variola virus.
Moreover, there are multiple sites conducting epidemiological analysis on the spread of the disease and its evolution as new variants arise. Like the public extinction of smallpox through a global coordinated effort of vaccination, it may be possible to drive the monkeypox virus into extinction with effective vaccination due to its relatively low virulence.
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{{cite web}}: |first= has generic name (help) The monkeypox virus (MPV, MPXV, or hMPXV), also called the mpox virus, 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 (VARV), cowpox (CPX), and vaccinia (VACV) 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. Symptoms of mpox in humans include a rash that forms blisters and then crusts over, fever, and swollen lymph nodes. The virus is transmissible between animals and humans by direct contact to the lesions or bodily fluids. The virus was given the name monkeypox virus after being isolated from monkeys, but most of the carriers of this virus are small mammals.
Variation in virulence of the virus has been observed in isolates from Central Africa, where strains are more virulent than those from Western Africa. The two areas have distinct clades of the virus, termed Clade I and Clade II. 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.
