Volume 30, Issue 2 (4-2023)                   RJMS 2023, 30(2): 10-24 | Back to browse issues page

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Razizadeh M H, Bouzari B, Tabibzadeh A, Saed S, Ajdarkosh H, Karbalaie Niya M H. A Comprehensive Review on Monkeypox. RJMS 2023; 30 (2) :10-24
URL: http://rjms.iums.ac.ir/article-1-7547-en.html
Department of Virology, Gastrointestinal and liver diseases research center, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran , mohamad.karbalai@yahoo.com
Abstract:   (798 Views)
Monkeypox is a smallpox-like viral infection caused by a virus of common origin between humans and animals, which belongs to the genus Orthopoxvirus, the Poxviridae family, and sub-family Chordopoxvirinae. The virus was first isolated in 1958 from a group of sick Macaca cynomolgus monkeys. Human infection with the monkeypox virus was first described in Central Africa in 1970 in a 9-month-old child from Zaire (1, 2). The disease is more common in the Congo basin countries of Africa and possibly West Africa, as well as the majority of human cases are reported from Congo basin countries (3, 4).
Smallpox is a serious, contagious, and sometimes fatal infectious disease, and its name in Latin means "speckled" and refers to bumps that appear on the skin of the affected person's face and body. Smallpox has been prevalent for thousands of years but has now been eradicated after a successful worldwide vaccination program. The last natural case in the world occurred in Somalia in 1977. After removing the disease from the world, routine vaccination against smallpox was stopped among the public because it was no longer necessary to prevent. In 1970, when an infection with smallpox was close to being eradicated, a previously unknown Orthopox virus called monkeypox was detected in humans. The first known human case in the Équateur province of the Democratic Republic of the Congo occurred when a 9-month-old infant contracted a smallpox-like disease that was eventually confirmed by the World Health Organization as monkeypox in humans (3). Other similar cases occurred in Ivory Coast, Libya, Nigeria, and Sierra Leone between 1970 and 1971, which were attributed to monkeypox infection (2).
The monkeypox virus was first isolated in 1958 from vesiculopustular lesions among monkeys kept at the Copenhagen State Serum Institute (5). The close resemblance between smallpox and smallpox in captive monkeys focused attention on the monkeypox virus as a potential threat to smallpox eradication.
Before 1970, monkeypox was known only in inhumane hosts. Between 1970 and 1986, 10 cases of monkeypox were reported in humans from West African countries (Sierra Leone, Nigeria, Libya, and Ivory Coast) and 394 cases from the Democratic Republic of the Congo, Cameroon and Central African Republic (2).
Monkeypox was limited to rainforests in central and West Africa until 2003 when the first cases were reported in the Western Hemisphere. In late spring 2003, several people in the U.S. Midwest were identified following exposure to meadow dogs (a rodent of the Cynomys species) infected with the monkeypox virus with a fever, rash, respiratory symptoms, and lymphadenopathy (6).
Genomic sequencing of monkeypox clades isolated from the United States, West and Central Africa has determined the presence of two distinct clade clades of the virus. U.S. isolates were identical to west African clades. The clinical course of the disease was milder among people infected with the West African clade with minimal transmission from human to human compared to those infected with clades in the Central African region (7). In 2010, using the animal model of the prairie dogs in a re-independent study, it was confirmed that the Congo Basin monkeypox virus clade was more malignant than the monkeypox virus clades in West Africa (8). Therefore, the aim of this study was to provide general information about virology, clinical, diagnostic, virulence, control, and treatment of this viral infection.
The Monkeypox virus belongs to the Poxviridae family, which also includes the bovine smallpox virus, vaccinia, and variola (smallpox). Poxviruses are the largest known vertebrate infecting viruses that infect humans and other vertebrates (subfamily Chondropoxvirinae species) as well as arthropods (subfamily Entemopoxvirinae species). There are about 70 known species of Poxviruses, classified in 28 genera and two subfamilies of Chordopoxvirinae and Entomopoxvirinae. The virions of these viruses contain the linear double-stranded deoxyribonucleic acid genome (dsDNA) and enzymes that synthesize messenger ribonucleic acid (mRNA). These viruses multiply in the cytoplasm of host cells (2).
The chordopoxvirinae subfamily contains about ten genera that are genetically and antigenic related. The orthopoxvirus genus of the virus includes camelpox, bovine pox, Ectromelia, monkeypox, raccoon pox, Skunkpox, gerbil pox, Uasin Gishu (horsepox virus), vaccinia, variola and Vel pox (a rodent resembling mice). Many smallpox viruses are associated with a particular vertebrate species, suggesting that transmission of these viruses preferably occurs among certain species of vertebrates. Although random transmission to different vertebrate species can occur, no clinical and pathological conditions have been observed in infected hosts leading to the preservation of the virus in these accidentally infected species (9). Orthopoxviruses that can infect humans include variola, vaccinia, bovine smallpox, and monkeypox virus. The variola virus only infects humans, and the Vaccinia virus is a vaccine clade that does not exist in nature and is used to vaccinate smallpox. The Vaccinia virus originated in the 18th century from an unknown vertebrate species. Bovine smallpox can infect cats and cows and transmit the infection to humans as well (2).
Monkeypox is also a rodent-infecting virus most seen in West and Central Africa. Unlike smallpox, the monkeypox virus can infect rabbit skin and can be serially transmitted through mouse inoculation. Four viral Orthopoxviruses that can infect humans cause macroscopic lesions on the inoculated chorioallantoic membrane of embryonic eggs (2). These viruses also differ in the ability to replicate in different tissue culture cells. Currently, however, the clearest results for recognizing differences have been obtained by restrictive patterns of viral DNA endonuclease (10). Some genetic differences have been observed between monkeypox viruses isolated from regions in west and central Africa. Genomic studies have shown strong evidence that the monkeypox virus is isolated from the ancestors of the variola virus. This is important because some researchers have been given the possibility that variola may evolve again from the monkeypox virus. Prior to the development of molecular methods, significant efforts were made to detect these four viruses using serological reactions. The results of these studies showed that these viruses share most antigens (11). Results were obtained using absorbed serum in agar diffusion gel test, but were quickly replaced by studies on biological characteristics and DNA limiting patterns. The development of relatively specific antigens has been very efficient for serological studies in humans and animals. For example, this is essential in the possible rapid diagnosis of infection caused by viruses belonging to the orthopox group of viruses, as well as differentiation from chickenpox, as it may cause confusion in adopting clinical measures. For this purpose, it is recommended that the shells of waste be sent to the diagnostic laboratory without a transfer device. Investigation of lesion shells with electron microscopy allows differentiation of orthopox and herpes viruses. Smallpox viruses can be detected in more than 95 percent of lesions, while the varicella-zoster virus can only be detected in half of the material from chickenpox cases. That means negative electron microscopy samples are highly unlikely to be infected with the monkeypox virus (2, 12, 13).
Poxviruses are one of the largest and most complex viruses (14). They are brick-shaped particles that vary in width from 220 nm to 450 nm in length and 140 nm to 260 nm in width (15). Therefore, the monkeypox virus is so large that it can be seen by light microscopy and its structure can be solved by electron microscopy. However, a higher-than-limit magnification provided by electron microscopy is required for its ultrastructural separation. The virion consists of four main elements: core, lateral objects, outer membrane, and outer lipoprotein coating. The central core contains double-stranded viral DNA (dsDNA) and core fibers and is surrounded by a solid layer of rod-shaped structures known as the palisade layer. The central nucleus, palisade layer, and lateral objects are enclosed by the outer membrane, which is composed of many surface tubules. Spontaneously released virions often have external lipoprotein coatings, while virions released by cell degradation lack this coating. An adult virion contains at least 80 viral proteins (16).  The monkeypox virus genome is a large linear molecule (197,000 open pairs) of dsDNA, ranked among the largest viral genomes (16). Each end of the genome contains identical but opposite-directional endings with a size of about 6,000 bp (17) with a set of short burst iterations (18) and end-series pin rings (19). The genome consists of about 190 non-overlapping open reading frames (ORF) (more than 180 base pairs in length), containing at least 60 amino acid residues. Of these, there are four in reverse terminal replication (17, 20). The content of guanine and cytosine DNA of the monkeypox virus is low and about 31.1% (21). The two distinct genetic categories of the monkeypox virus include the clades of West Africa and Central Africa (16).
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Type of Study: review article | Subject: Microbiology

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