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Microbiology Spectrum Aug 2016Smallpox is considered among the most devastating of human diseases. Its spread in populations, initiated for thousands of years following a probable transmission from... (Review)
Review
Smallpox is considered among the most devastating of human diseases. Its spread in populations, initiated for thousands of years following a probable transmission from an animal host, was concomitant with movements of people across regions and continents, trade and wars. Literature permitted to retrace the occurrence of epidemics from ancient times to recent human history, smallpox having affected all levels of past society including famous monarchs. The disease was officially declared eradicated in 1979 following intensive vaccination campaigns.Paleomicrobiology dedicated to variola virus is restricted to few studies, most unsuccessful, involving ancient material. Only one recent approach allowed the identification of viral DNA fragments from lung tissue of a 300-year-old body excavated from permafrost in Eastern Siberia; phylogenetic analysis revealed that this ancient strain was distinct from those described during the 20th century.
Topics: Animals; Disease Transmission, Infectious; Epidemics; Global Health; History, 15th Century; History, 16th Century; History, 17th Century; History, 18th Century; History, 19th Century; History, 20th Century; History, Ancient; History, Medieval; Human Migration; Humans; Paleopathology; Poxviridae; Smallpox; Travel; Virology
PubMed: 27726788
DOI: 10.1128/microbiolspec.PoH-0004-2014 -
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 -
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 -
Cell Oct 2016Monkeypox (MPXV) and cowpox (CPXV) are emerging agents that cause severe human infections on an intermittent basis, and variola virus (VARV) has potential for use as an...
Monkeypox (MPXV) and cowpox (CPXV) are emerging agents that cause severe human infections on an intermittent basis, and variola virus (VARV) has potential for use as an agent of bioterror. Vaccinia immune globulin (VIG) has been used therapeutically to treat severe orthopoxvirus infections but is in short supply. We generated a large panel of orthopoxvirus-specific human monoclonal antibodies (Abs) from immune subjects to investigate the molecular basis of broadly neutralizing antibody responses for diverse orthopoxviruses. Detailed analysis revealed the principal neutralizing antibody specificities that are cross-reactive for VACV, CPXV, MPXV, and VARV and that are determinants of protection in murine challenge models. Optimal protection following respiratory or systemic infection required a mixture of Abs that targeted several membrane proteins, including proteins on enveloped and mature virion forms of virus. This work reveals orthopoxvirus targets for human Abs that mediate cross-protective immunity and identifies new candidate Ab therapeutic mixtures to replace VIG.
Topics: Antibodies, Monoclonal; Antibodies, Neutralizing; Antibodies, Viral; Antibody Specificity; Cowpox; Cowpox virus; Cross Reactions; Humans; Leukocytes, Mononuclear; Mpox (monkeypox); Monkeypox virus; Poxviridae Infections; Smallpox; Vaccinia; Vaccinia virus; Variola virus
PubMed: 27768891
DOI: 10.1016/j.cell.2016.09.049 -
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 -
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 -
International Journal of Molecular... Jul 2022The global vaccination programme against smallpox led to its successful eradication and averted millions of deaths. Monkeypox virus (MPXV) is a close relative of the... (Review)
Review
The global vaccination programme against smallpox led to its successful eradication and averted millions of deaths. Monkeypox virus (MPXV) is a close relative of the Variola (smallpox) virus. Due to antigenic similarity, smallpox vaccines cross-protect against MPXV. However, over 70% of people living today were never vaccinated against smallpox. Symptoms of monkeypox (MPX) include fever, head- and muscle ache, lymphadenopathy and a characteristic rash that develops into papules, vesicles and pustules which eventually scab over and heal. MPX is less often fatal (case fatality rates range from <1% to up to 11%) than smallpox (up to 30%). MPXV is endemic in sub-Saharan Africa, infecting wild animals and causing zoonotic outbreaks. Exotic animal trade and international travel, combined with the increasing susceptibility of the human population due to halted vaccination, facilitated the spread of MPXV to new areas. The ongoing outbreak, with >10,000 cases in >50 countries between May and July 2022, shows that MPXV can significantly spread between people and may thus become a serious threat to public health with global consequences. Here, we summarize the current knowledge about this re-emerging virus, discuss available strategies to limit its spread and pathogenicity and evaluate its risk to the human population.
Topics: Animals; Humans; Mpox (monkeypox); Monkeypox virus; Smallpox
PubMed: 35887214
DOI: 10.3390/ijms23147866 -
Cleveland Clinic Journal of Medicine Mar 2023The monkeypox (mpox) epidemic was declared a global health emergency in July 2022. The mpox virus belongs to the same virus family as the smallpox, or variola virus, but... (Review)
Review
The monkeypox (mpox) epidemic was declared a global health emergency in July 2022. The mpox virus belongs to the same virus family as the smallpox, or variola virus, but the infection is a less lethal threat than smallpox. Nevertheless, its relationship to smallpox is a worldwide concern, as is the discontinuation of universal smallpox vaccinations since the 1980s. Newer therapies and vaccines are available for both infections, including 2 antiviral drugs that can be used under certain conditions. Two vaccines have been developed for mpox prevention, but clarity is needed on when and how to use them. Preventive public health measures and prioritization of resources for managing infectious disease are concerns.
Topics: Humans; Smallpox; Variola virus; Mpox (monkeypox); Antiviral Agents; Epidemics
PubMed: 36858615
DOI: 10.3949/ccjm.90a.22067