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Immunological Reviews Oct 2008Monkeypox is a disease that is endemic in Central and Western Africa. However, in 2003, there was an outbreak in the United States, representing the first documented... (Review)
Review
Monkeypox is a disease that is endemic in Central and Western Africa. However, in 2003, there was an outbreak in the United States, representing the first documented monkeypox cases in the Western hemisphere. Although monkeypox virus is less fatal and not as transmissible as variola virus, the causative agent of smallpox, there is concern that monkeypox virus could become a more efficient human pathogen. The reason for this may lie in the virus' genetic makeup, ecological changes, changes in host behavior, and the fact that with the eradication of variola virus, routine smallpox vaccination is no longer carried out. In this review, we focus on the viral proteins that are predicted to modulate the host immune response and compare the genome of monkeypox virus with the genomes of variola virus and the vaccinia virus, the orthopoxvirus that represented the smallpox vaccine. There are differences found in several of these immune-modulating genes including genes that express proteins that affect cytokines such as interleukin-1, tumor necrosis factor, and interferon. There are also differences in genes that code for virulence factors and host range proteins. Genetic differences likely also explain the differences in virulence between two strains of monkeypox virus found in two different regions of Africa. In the current setting of limited smallpox vaccination and little orthopoxvirus immunity in parts of the world, monkeypox could become a more efficient human pathogen under the right circumstances.
Topics: Animals; Humans; Mpox (monkeypox); Monkeypox virus; Phylogeny; Vaccinia virus; Variola virus; Viral Proteins
PubMed: 18837778
DOI: 10.1111/j.1600-065X.2008.00691.x -
Viruses Jan 2020Widespread vaccination programmes led to the global eradication of smallpox, which was certified by the World Health Organisation (WHO), and, since 1978, there has been... (Review)
Review
Widespread vaccination programmes led to the global eradication of smallpox, which was certified by the World Health Organisation (WHO), and, since 1978, there has been no case of smallpox anywhere in the world. However, the viable variola virus (VARV), the causative agent of smallpox, is still kept in two maximum security laboratories in Russia and the USA. Despite the eradication of the disease smallpox, clandestine stocks of VARV may exist. In a rapidly changing world, the impact of an intentional VARV release in the human population would nowadays result in a public health emergency of global concern: vaccination programmes were abolished, the percentage of immunosuppressed individuals in the human population is higher, and an increased intercontinental air travel allows for the rapid viral spread of diseases around the world. The WHO has authorised the temporary retention of VARV to enable essential research for public health benefit to take place. This work aims to develop diagnostic tests, antiviral drugs, and safer vaccines. Advances in synthetic biology have made it possible to produce infectious poxvirus particles from chemicals in vitro so that it is now possible to reconstruct VARV. The status of smallpox in the post-eradication era is reviewed.
Topics: Antiviral Agents; Biohazard Release; Disease Eradication; Evolution, Molecular; Genome, Viral; Humans; Immunization Programs; Risk; Smallpox; Smallpox Vaccine; Synthetic Biology; Variola virus; World Health Organization
PubMed: 31991671
DOI: 10.3390/v12020138 -
The Journal of Infectious Diseases Sep 2021
Topics: History, 20th Century; History, 21st Century; Humans; Population Surveillance; Smallpox; Smallpox Vaccine; Vaccination; Variola virus
PubMed: 34590143
DOI: 10.1093/infdis/jiaa588 -
FEBS Letters Nov 2001Monkeypox virus (MPV) causes a human disease which resembles smallpox but with a lower person-to-person transmission rate. To determine the genetic relationship between...
Monkeypox virus (MPV) causes a human disease which resembles smallpox but with a lower person-to-person transmission rate. To determine the genetic relationship between the orthopoxviruses causing these two diseases, we sequenced the 197-kb genome of MPV isolated from a patient during a large human monkeypox outbreak in Zaire in 1996. The nucleotide sequence within the central region of the MPV genome, which encodes essential enzymes and structural proteins, was 96.3% identical with that of variola (smallpox) virus (VAR). In contrast, there were considerable differences between MPV and VAR in the regions encoding virulence and host-range factors near the ends of the genome. Our data indicate that MPV is not the direct ancestor of VAR and is unlikely to naturally acquire all properties of VAR.
Topics: Amino Acid Sequence; Ankyrins; Evolution, Molecular; Genome, Viral; Humans; Models, Genetic; Molecular Sequence Data; Monkeypox virus; Open Reading Frames; Phylogeny; Protein Structure, Tertiary; Sequence Homology, Amino Acid; Variola virus; Virulence
PubMed: 11734207
DOI: 10.1016/s0014-5793(01)03144-1 -
Viruses Dec 2023Smallpox was a highly contagious disease caused by the variola virus. The disease affected millions of people over thousands of years and variola virus ranked as one of... (Review)
Review
Smallpox was a highly contagious disease caused by the variola virus. The disease affected millions of people over thousands of years and variola virus ranked as one of the deadliest viruses in human history. The complete eradication of smallpox in 1980, a major triumph in medicine, was achieved through a global vaccination campaign using a less virulent poxvirus, vaccinia virus. Despite this success, the herd immunity established by this campaign has significantly waned, and concerns are rising about the potential reintroduction of variola virus as a biological weapon or the emergence of zoonotic poxviruses. These fears were further fueled in 2022 by a global outbreak of monkeypox virus (mpox), which spread to over 100 countries, thereby boosting interest in developing new vaccines using molecular approaches. However, poxviruses are complex and creating modern vaccines against them is challenging. This review focuses on the structural biology of the six major neutralization determinants on poxviruses (D8, H3, A27, L1, B5, and A33), the localization of epitopes targeted by neutralizing antibodies, and their application in the development of subunit vaccines.
Topics: Humans; Poxviridae; Smallpox; Vaccinia virus; Smallpox Vaccine; Variola virus
PubMed: 38140637
DOI: 10.3390/v15122396 -
Viruses Dec 2022Considering that vaccination against smallpox with live vaccinia virus led to serious adverse effects in some cases, the WHO, after declaration of the global eradication... (Review)
Review
Considering that vaccination against smallpox with live vaccinia virus led to serious adverse effects in some cases, the WHO, after declaration of the global eradication of smallpox in 1980, strongly recommended to discontinue the vaccination in all countries. This led to the loss of immunity against not only smallpox but also other zoonotic orthopoxvirus infections in humans over the past years. An increasing number of human infections with zoonotic orthopoxviruses and, first of all, monkeypox, force us to reconsider a possible re-emergence of smallpox or a similar disease as a result of natural evolution of these viruses. The review contains a brief analysis of the results of studies on genomic organization and evolution of human pathogenic orthopoxviruses, development of modern methods for diagnosis, vaccination, and chemotherapy of smallpox, monkeypox, and other zoonotic human orthopoxvirus infections.
Topics: Animals; Humans; Smallpox; Mpox (monkeypox); Variola virus; Poxviridae Infections; Orthopoxvirus; Zoonoses; Monkeypox virus
PubMed: 36680142
DOI: 10.3390/v15010103 -
Clinical Microbiology and Infection :... Mar 2014Smallpox is an infectious disease that is unique to humans, caused by a poxvirus. It is one of the most lethal of diseases; the virus variant Variola major has a... (Review)
Review
Smallpox is an infectious disease that is unique to humans, caused by a poxvirus. It is one of the most lethal of diseases; the virus variant Variola major has a mortality rate of 30%. People surviving this disease have life-long consequences, but also assured immunity. Historically, smallpox was recognized early in human populations. This led to prevention attempts--variolation, quarantine, and the isolation of infected subjects--until Jenner's discovery of the first steps of vaccination in the 18th century. After vaccination campaigns throughout the 19th and 20th centuries, the WHO declared the eradication of smallpox in 1980. With the development of microscopy techniques, the structural characterization of the virus began in the early 20th century. In 1990, the genomes of different smallpox viruses were determined; viruses could be classified in order to investigate their origin, diffusion, and evolution. To study the evolution and possible re-emergence of this viral pathogen, however, researchers can only use viral genomes collected during the 20th century. Cases of smallpox in ancient periods are sometimes well documented, so palaeomicrobiology and, more precisely, the study of ancient smallpox viral strains could be an exceptional opportunity. The analysis of poxvirus fragmented genomes could give new insights into the genetic evolution of the poxvirus. Recently, small fragments of the poxvirus genome were detected. With the genetic information obtained, a new phylogeny of smallpox virus was described. The interest in conducting studies on ancient strains is discussed, in order to explore the natural history of this disease.
Topics: Animals; Biological Evolution; History, 16th Century; History, 17th Century; History, 18th Century; History, 19th Century; History, 20th Century; Humans; Smallpox; Variola virus
PubMed: 24438205
DOI: 10.1111/1469-0691.12536 -
Revue Scientifique Et Technique... Apr 2000During and after the smallpox eradication campaign, human cases of monkeypox appeared in West and Central Africa, as isolated cases or as small epidemics. Since... (Review)
Review
During and after the smallpox eradication campaign, human cases of monkeypox appeared in West and Central Africa, as isolated cases or as small epidemics. Since inter-human transmission has never or only very exceptionally been documented, monkeypox does not represent a serious threat to humans. The virus reservoir is among tree squirrels living in the tropical rain forests of Africa and humans are infected by hunting, killing and skinning these animals. However, the modernization of society lessens human contact with the virus reservoir. Since the eradication of smallpox, stocks of variola virus have been maintained; whether these stocks should now be destroyed is a political question, which is seriously compromised by mistrust between countries.
Topics: Animals; Humans; Monkeypox virus; Poxviridae Infections; Primates; Public Health; Smallpox; Zoonoses
PubMed: 11189729
DOI: 10.20506/rst.19.1.1207