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Current Biology : CB Oct 2020The ability to sequence genomes from ancient biological material has provided a rich source of information for evolutionary biology and engaged considerable public... (Review)
Review
The ability to sequence genomes from ancient biological material has provided a rich source of information for evolutionary biology and engaged considerable public interest. Although most studies of ancient genomes have focused on vertebrates, particularly archaic humans, newer technologies allow the capture of microbial pathogens and microbiomes from ancient and historical human and non-human remains. This coming of age has been made possible by techniques that allow the preferential capture and amplification of discrete genomes from a background of predominantly host and environmental DNA. There are now near-complete ancient genome sequences for three pathogens of considerable historical interest - pre-modern bubonic plague (Yersinia pestis), smallpox (Variola virus) and cholera (Vibrio cholerae) - and for three equally important endemic human disease agents - Mycobacterium tuberculosis (tuberculosis), Mycobacterium leprae (leprosy) and Treponema pallidum pallidum (syphilis). Genomic data from these pathogens have extended earlier work by paleopathologists. There have been efforts to sequence the genomes of additional ancient pathogens, with the potential to broaden our understanding of the infectious disease burden common to past populations from the Bronze Age to the early 20 century. In this review we describe the state-of-the-art of this rapidly developing field, highlight the contributions of ancient pathogen genomics to multidisciplinary endeavors and describe some of the limitations in resolving questions about the emergence and long-term evolution of pathogens.
Topics: Animals; Bacteria; Biological Evolution; DNA, Ancient; DNA, Bacterial; Evolution, Molecular; Genome; Genome, Bacterial; Genomics; Humans; Microbiota; Mycobacterium leprae; Mycobacterium tuberculosis; Phylogeny; Treponema; Variola virus; Vibrio cholerae; Yersinia pestis
PubMed: 33022266
DOI: 10.1016/j.cub.2020.08.081 -
Viruses Dec 2019Two distinct phenomena of airborne transmission of variola virus (smallpox) were described in the pre-eradication era-direct respiratory transmission, and a unique... (Review)
Review
Two distinct phenomena of airborne transmission of variola virus (smallpox) were described in the pre-eradication era-direct respiratory transmission, and a unique phenomenon of transmission over greater distances, referred to as "aerial convection". We conducted an analysis of data obtained from a systematic review following the PRISMA criteria, on the long-distance transmission of smallpox. Of 8179 studies screened, 22 studies of 17 outbreaks were identified-12 had conclusive evidence of aerial convection and five had partially conclusive evidence. Aerial convection was first documented in 1881 in England, when smallpox incidence had waned substantially following mass vaccination, making unusual transmissions noticeable. National policy at the time stipulated spatial separation of smallpox hospitals from other buildings and communities. The evidence supports the transmission of smallpox through aerial convection at distances ranging from 0.5 to 1 mile, and one instance of 15 km related to bioweapons testing. Other explanations are also possible, such as missed chains of transmission, fomites or secondary aerosolization from contaminated material such as bedding. The window of observation of aerial convection was within the 100 years prior to eradication. Aerial convection appears unique to the variola virus and is not considered in current hospital infection control protocols. Understanding potential aerial convection of variola should be an important consideration in planning for smallpox treatment facilities and protecting potential contacts and surrounding communities.
Topics: Air Microbiology; Convection; Disease Outbreaks; England; Humans; Smallpox; Smallpox Vaccine; Systematic Reviews as Topic; Variola virus
PubMed: 31892158
DOI: 10.3390/v12010033 -
Clinical Microbiology and Infection :... Dec 2023The 2022 mpox outbreak drew global attention to this neglected pathogen. While most of the world was taken by surprise, some countries have seen this pathogen emerge and... (Review)
Review
BACKGROUND
The 2022 mpox outbreak drew global attention to this neglected pathogen. While most of the world was taken by surprise, some countries have seen this pathogen emerge and become endemic several decades prior to this epidemic.
OBJECTIVES
This narrative review provides an overview of mpox epidemiology since its discovery through the 2022 global outbreak.
SOURCES
We searched PubMed for relevant literature about mpox epidemiology and transmission through 28 February 2023.
CONTENT
The emergence of human mpox is intertwined with the eradication of smallpox and the cessation of the global smallpox vaccination campaign. The first human clade I and II monkeypox virus (MPXV) infections were reported as zoonoses in Central and West Africa, respectively, around 1970 with sporadic infections reported throughout the rest of the decade. Over the next five decades, Clade I MPXV was more common and caused outbreaks of increasing size and frequency, mainly in the Democratic Republic of the Congo. Clade II MPXV was rarely observed, until its re-emergence and ongoing transmission in Nigeria, since 2017. Both clades showed a shift from zoonotic to human-to-human transmission, with potential transmission through sexual contact being observed in Nigeria. In 2022, clade II MPXV caused a large human outbreak which to date has caused over 86,000 cases in 110 countries, with strong evidence of transmission during sexual contact. By February 2023, the global epidemic has waned in most countries, but endemic regions continue to suffer from mpox.
IMPLICATIONS
The changing epidemiology of mpox demonstrates how neglected zoonosis turned into a global health threat within a few decades. Thus, mpox pathophysiology and transmission dynamics need to be further investigated, and preventive and therapeutic interventions need to be evaluated. Outbreak response systems need to be strengthened and sustained in endemic regions to reduce the global threat of mpox.
Topics: Animals; Humans; Smallpox; Mpox (monkeypox); Variola virus; Zoonoses; Disease Outbreaks
PubMed: 37574113
DOI: 10.1016/j.cmi.2023.08.008 -
Vaccine Aug 2021Smallpox, a disease caused by the variola virus, is one of the most dangerous diseases and had killed numerous people before it was eradicated in 1980. However, smallpox...
Smallpox, a disease caused by the variola virus, is one of the most dangerous diseases and had killed numerous people before it was eradicated in 1980. However, smallpox has emerged as the most threatening bio-terrorism agent; as the first- and second-generation smallpox vaccines have been controversial and have caused severe adverse reactions, new demands for safe smallpox vaccines have been raised and some attenuated smallpox vaccines have been developed. We have developed a cell culture-based highly attenuated third-generation smallpox vaccine candidate KVAC103 strain by 103 serial passages of the Lancy-Vaxina strain derived from the Lister in Vero cells. Several clones were selected, taking into consideration their shape, size, and growth rate in mammalian cells. The clones were then inoculated intracerebrally in suckling mice to test for neurovirulence by observing survival. Protective immune responses in adult mice were examined by measuring the levels of neutralization antibodies and IFN-γ expression. Among several clones, clone 7 was considered the best alternative candidate because there was no mortality in suckling mice against a lethal challenge. In addition, enhanced neutralizing antibodies and T-cell mediated IFN-γ production were observed in clone 7-immunized mice. Clone 7 was named "KVAC103" and was used for the skin toxicity test and full-genome analysis. KVAC103-inoculated rabbits showed reduced skin lesions compared to those inoculated with the Lister strain, Lancy-Vaxina. A whole genome analysis of KVAC103 revealed two major deleted regions that might contribute to the reduced virulence of KVAC103 compared to the Lister strain. Phylogenetic inference supported the close relationship with the Lister strain. Collectively, our data demonstrate that KVAC103 holds promise for use as a third-generation smallpox vaccine strain due to its enhanced safety and efficacy.
Topics: Animals; Antibodies, Viral; Chlorocebus aethiops; Mice; Mice, Inbred BALB C; Phylogeny; Rabbits; Smallpox; Smallpox Vaccine; Vaccines, Attenuated; Vaccinia virus; Variola virus; Vero Cells
PubMed: 34334254
DOI: 10.1016/j.vaccine.2021.06.060 -
Vaccine Dec 2017For almost 150 years after Edward Jenner had published the "Inquiry" in 1798, it was generally assumed that the cowpox virus was the vaccine against smallpox. It was... (Review)
Review
Equination (inoculation of horsepox): An early alternative to vaccination (inoculation of cowpox) and the potential role of horsepox virus in the origin of the smallpox vaccine.
For almost 150 years after Edward Jenner had published the "Inquiry" in 1798, it was generally assumed that the cowpox virus was the vaccine against smallpox. It was not until 1939 when it was shown that vaccinia, the smallpox vaccine virus, was serologically related but different from the cowpox virus. In the absence of a known natural host, vaccinia has been considered to be a laboratory virus that may have originated from mutational or recombinational events involving cowpox virus, variola viruses or some unknown ancestral Orthopoxvirus. A favorite candidate for a vaccinia ancestor has been the horsepox virus. Edward Jenner himself suspected that cowpox derived from horsepox and he also believed that "matter" obtained from either disease could be used as preventative of smallpox. During the 19th century, inoculation with cowpox (vaccination) was used in Europe alongside with inoculation with horsepox (equination) to prevent smallpox. Vaccine-manufacturing practices during the 19th century may have resulted in the use of virus mixtures, leading to different genetic modifications that resulted in present-day vaccinia strains. Horsepox, a disease previously reported only in Europe, has been disappearing on that continent since the beginning of the 20th century and now seems to have become extinct, although the virus perhaps remains circulating in an unknown reservoir. Genomic sequencing of a horsepox virus isolated in Mongolia in 1976 indicated that, while closely related to vaccinia, this horsepox virus contained additional, potentially ancestral sequences absent in vaccinia. Recent genetic analyses of extant vaccinia viruses have revealed that some strains contain ancestral horsepox virus genes or are phylogenetically related to horsepox virus. We have recently reported that a commercially produced smallpox vaccine, manufactured in the United States in 1902, is genetically highly similar to horsepox virus, providing a missing link in this 200-year-old mystery.
Topics: Animals; Cowpox; Genome, Viral; High-Throughput Nucleotide Sequencing; History, 18th Century; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Orthopoxvirus; Phylogeny; Smallpox; Smallpox Vaccine; Vaccination; Vaccinia virus; Variola virus
PubMed: 29137821
DOI: 10.1016/j.vaccine.2017.11.003 -
Virus Research Dec 2022First described in 1958, the human monkeypox virus (hMPXV) is a neglected zoonotic pathogen closely associated with the smallpox virus. The virus usually spreads via...
First described in 1958, the human monkeypox virus (hMPXV) is a neglected zoonotic pathogen closely associated with the smallpox virus. The virus usually spreads via close contact with the infected animal or human and has been endemic mostly in parts of the African continent. However, with the recent increase in trade, tourism, and travel, the virus has caused outbreaks in countries outside Africa. The recent outbreak in 2022 has been puzzling given the lack of epidemiological connection and the possible sexual transmission of the virus. Furthermore, there is limited understanding of the structural and pathogenetic mechanisms that are employed by the virus to invade the host cells. Henceforth, it is critical to understand the working apparatus governing the viral-immune interactions to develop effective therapeutical and prophylactic modalities. Hence, in the present short communication, we summarize the previously reported research findings regarding the virology of the human monkeypox virus.
Topics: Animals; Humans; Monkeypox virus; Mpox (monkeypox); Variola virus; Disease Outbreaks; Africa
PubMed: 36165924
DOI: 10.1016/j.virusres.2022.198932 -
Emerging Infectious Diseases Apr 2011In 2011, the World Health Organization will recommend the fate of existing smallpox stockpiles, but circumstances have changed since the complete destruction of these... (Review)
Review
In 2011, the World Health Organization will recommend the fate of existing smallpox stockpiles, but circumstances have changed since the complete destruction of these cultures was first proposed. Recent studies suggest that variola and its experimental surrogate, vaccinia, have a remarkable ability to modify the human immune response through complex mechanisms that scientists are only just beginning to unravel. Further study that might require intact virus is essential. Moreover, modern science now has the capability to recreate smallpox or a smallpox-like organism in the laboratory in addition to the risk of nature re-creating it as it did once before. These factors strongly suggest that relegating smallpox to the autoclave of extinction would be ill advised.
Topics: Animals; Health Policy; Humans; Russia; Smallpox; Smallpox Vaccine; United States; Variola virus; World Health Organization
PubMed: 21470459
DOI: 10.3201/eid1704.101865 -
Microbes and Infection Sep 2003Variola virus, the causative agent of smallpox, encodes approximately 200 proteins. Over 80 of these proteins are located in the terminal regions of the genome, where... (Review)
Review
Variola virus, the causative agent of smallpox, encodes approximately 200 proteins. Over 80 of these proteins are located in the terminal regions of the genome, where proteins associated with host immune evasion are encoded. To date, only two variola proteins have been characterized. Both are located in the terminal regions and demonstrate immunoregulatory functions. One protein, the smallpox inhibitor of complement enzymes (SPICE), is homologous to a vaccinia virus virulence factor, the vaccinia virus complement-control protein (VCP), which has been found experimentally to be expressed early in the course of vaccinia infection. Both SPICE and VCP are similar in structure and function to the family of mammalian complement regulatory proteins, which function to prevent inadvertent injury to adjacent cells and tissues during complement activation. The second variola protein is the variola virus high-affinity secreted chemokine-binding protein type II (CKBP-II, CBP-II, vCCI), which binds CC-chemokine receptors. The vaccinia homologue of CKBP-II is secreted both early and late in infection. CKBP-II proteins are highly conserved among orthopoxviruses, sharing approximately 85% homology, but are absent in eukaryotes. This characteristic sets it apart from other known virulence factors in orthopoxviruses, which share sequence homology with known mammalian immune regulatory gene products. Future studies of additional variola proteins may help illuminate factors associated with its virulence, pathogenesis and strict human tropism. In addition, these studies may also assist in the development of targeted therapies for the treatment of both smallpox and human immune-related diseases.
Topics: Animals; DNA, Viral; Genome, Viral; Humans; Receptors, Complement; Smallpox; Variola virus; Viral Proteins; Virulence
PubMed: 12941397
DOI: 10.1016/s1286-4579(03)00194-1 -
Emerging Infectious Diseases Feb 2005We reviewed historical data from 2 smallpox outbreaks in Liverpool and Edinburgh during the early and middle years of the 20th century to assess their contribution to... (Review)
Review
We reviewed historical data from 2 smallpox outbreaks in Liverpool and Edinburgh during the early and middle years of the 20th century to assess their contribution to developing modern strategies for response to a deliberate release of smallpox virus. Reports contemporaneous to these outbreaks provide detail on the effectiveness of public health interventions. In both outbreaks, extensive contact tracing, quarantine, and staged vaccination campaigns were initiated, and the outbreaks were controlled within 15 months and 3 months, respectively. In Edinburgh, the number of fatalities associated with vaccination exceeded the number of deaths from the disease. In Liverpool, ambulatory, vaccine-modified cases and misdiagnosis as chickenpox resulted in problems with outbreak control. The relatively slow spread of smallpox, as exemplified by the report from Liverpool, allowed for effective implementation of targeted intervention methods. Targeted surveillance and containment interventions have been successful in the past and should be explored as alternatives to mass vaccination.
Topics: Adolescent; Adult; Child; Child, Preschool; Disease Outbreaks; Humans; Infant; Middle Aged; Smallpox; Smallpox Vaccine; United Kingdom; Vaccination; Variola virus
PubMed: 15752449
DOI: 10.3201/eid1102.040609 -
Viruses May 2023Notwithstanding the presence of a smallpox vaccine that is effective against monkeypox (mpox), developing a universal vaccine candidate against monkeypox virus (MPXV) is...
Notwithstanding the presence of a smallpox vaccine that is effective against monkeypox (mpox), developing a universal vaccine candidate against monkeypox virus (MPXV) is highly required as the mpox multi-country outbreak has increased global concern. MPXV, along with variola virus (VARV) and vaccinia virus (VACV), belongs to the Orthopoxvirus genus. Due to the genetic similarity of antigens in this study, we have designed a potentially universal mRNA vaccine based on conserved epitopes that are specific to these three viruses. In order to design a potentially universal mRNA vaccine, antigens A29, A30, A35, B6, and M1 were selected. The conserved sequences among the three viral species-MPXV, VACV, and VARV-were detected, and B and T cell epitopes containing the conserved elements were used for the design of the multi-epitope mRNA construct. Immunoinformatics analyses demonstrated the stability of the vaccine construct and optimal binding to MHC molecules. Humoral and cellular immune responses were induced by immune simulation analyses. Eventually, based on in silico analysis, the universal mRNA multi-epitope vaccine candidate designed in this study may have a potential protection against MPXV, VARV, and VACV that will contribute to the advancement of prevention strategies for unpredictable pandemics.
Topics: Humans; Vaccinia virus; Variola virus; Smallpox; Mpox (monkeypox); Epitopes; Smallpox Vaccine; Monkeypox virus; mRNA Vaccines
PubMed: 37243206
DOI: 10.3390/v15051120