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At least 19 recordsLinked to original sources
PubMed1979

Conservation and variation in Orthopoxvirus genome structure.

Orthopoxvirus DNA from representative strains of rabbitpox, vaccinia, monkeypox, variola, cowpox and ectromelia viruses was analysed by cleavage with restriction endonucleases HindIII, XhoI or SmaI. Genome mol. wt. vary from about 120 x 10(6) for rabbitpox to about 145 x 10(6) for cowpox. Physical maps of cleavage sites are similar and characteristic for strains of the same Orthopoxvirus type. The distribution of HindIII sites suggests that an internal region of mol. wt. about 30 x 10(6) is highly conserved between Orthopoxvirus genomes although some type-specific differences occur within this region, especially with strains of ectromelia virus. Conservation of internal sequences is less marked following analysis with XhoI although cleavages within this central region of particular genomes appear to represent a subset of preferred sites. Endonuclease SmaI cleaves exceptionally infrequently and distinguishes variola, monkeypox, vaccinia, cowpox or ectromelia viruses. Type specific differences result largely from extensive, near terminal variations in length and sequence. Representative Orthopoxvirus genomes have rapidly renaturing terminal restriction fragments confirming the presence of near terminal, covalent cross-links. Terminal restriction fragments from the same or different genomes generally cross hybridize indicating the presence of near terminal repetitions of mol. wt. up to 6 x 10(6) and which share at least a subset of common sequences. Variola strains however, appear to lack such sequences from one specific terminus which maps shorter than that of related viruses.

Base Sequence↗
PubMed2025

Bioluminescence Imaging to Study Recombinant Orthopoxvirus Infection in Animal Models.

Bioluminescent images of viral replication in live animals (in vivo) reveal disease dynamics and effects of medical countermeasures over time. After selecting an appropriate orthopoxvirus animal model for the study, a recombinant virus with the firefly luciferase gene inserted in the genome is used to infect the animals. On the day of bioluminescent imaging, the substrate, D-luciferin, is prepared; animals are sedated and injected with the substrate and IVIS imager is utilized; various bioluminescent images are acquired; then animals recover and are able to continue in the study. Ex vivo imaging can also be completed after animals are euthanized at experimental endpoint. This approach allows real-time imaging of viral kinetics within an animal, and analysis of images can provide an additional quantitative measure throughout the study. Bioluminescent imaging not only provides scientific benefits but also benefits to animal welfare. For these reasons, bioluminescent imaging should be considered for any in vivo orthopoxvirus study.

Animals↗
PubMedDate not supplied

[Possible mechanism of orthopoxvirus preservation in nature].

Until recently, virus carrier state in the absence of overt clinical infection has been known for only one species of orthopoxviruses, namely, ectromelia virus. The paper describes the results of the modelling of asypmtomatic infection caused by monkeypox, cowpox, and ratpox viruses. Persistence of these viruses up to 6 weeks in animals (hamsters, cotton and white rats) with experimental asymptomatic infection as well as in apparently normal naturally infected white rats was established by isolation of virus from the organs of these animals. These results suggest that asymptomatic virus carrier state may occur both with ectromelia and a number of other orthopoxviruses. The mechanism may be of ecological importance, providing for circulation of these viruses and their preservation as biological species in nature.

Animals↗
PubMed2025

Orthopoxvirus Genome Sequencing, Assembly, and Analysis.

Poxviruses have exceptionally large genomes compared to most other viruses, which represent unique challenges to sequencing and assembly due to complex features such as repeat elements and low complexity sequences. The 2022 global mpox outbreak led to an unprecedented level of poxvirus sequencing as public health and research institutions faced with large sample numbers and demand for fast turnaround, merged NGS protocols designed for small RNA viruses with poxvirus expertise. Traditional manual assembly, checking, and editing of genomes was not feasible. Here, we present a protocol for metagenomic sequencing and orthopoxvirus genome assembly directly from DNA extracted from a patient lesion swab with no viral enrichment or host depletion. This sequencing approach is cost effective when using high throughput sequencing instruments and allows for detection of genomic insertions, deletions, and large rearrangement with confidence. We describe usage of two publicly available bioinformatic pipelines for genome assembly, quality control, annotation, and submission to sequence repositories.

Orthopoxvirus↗
PubMed1979

Structural polypeptides of Orthopoxvirus: their distribution in various members and location within the virion.

The structural polypeptides of accepted species and recently isolated members of the genus Orthopoxvirus have been examined by SDS-polyacrylamide gel electrophoresis. The viruses shared many polypeptides but some differences were found. The viruses could be divided into a vaccinia group (including buffalopox, 'Lenny' and MK-10), an ectromelia group (including elephant virus and Moscow virus), cowpox, camelpox and monkeypox. Minor differences were found in the polypeptides of monkeypox virus strains from human and monkey outbreaks. Controlled degradation of virions showed that the polypeptides which enabled the viruses to be differentiated were located in the surface and sub-surface layers. The cores of the viruses all gave the same complex polypeptide pattern.

Animals↗
PubMed1979

Orthopoxvirus strains defective in surface antigen induction.

Various strains of vaccinia, variola, whitepox, monkeypox and cowpox viruses were examined for their capacity to induce a specific early antigen detectable on the surface of infected cells. The Elstree strain of vaccinia, two strains of variola minor and white variants of cowpox and monkeypox viruses lacked the capacity to induce the antigen. Variation of the parent cowpox and monkeypox viruses to white variants was always accompanied by the loss of the antigen-inducing capacity.

Animals↗
PubMed1977

Serological relatedness of monkeypox, variola, and vaccinia viruses.

Closely related human and monkey orthopoxviruses were differentiated by serologic techniques. Antiviral sera were tested by immunodiffusion for reactivity against six different viral antigens prepared from either infected cell cultures or infected chorioallantoic membranes (CAMs) of embryonated eggs. Portions of each antiserum were separately absorbed with heterologous antigens from infected CAMs to remove common reactivity. The absorbed sera formed immunodiffusion precipitates with both types of antigen preparation and revealed specific-character differences that made it possible to classify the viruses as variola, vaccinia, or monkeypox. Cross-complement fixation tests were also used to examine the immunologic reactivities of antisera to detergent-treated, purified preparations of three orthopoxviruses. Only common reactivities were detected by this method, however, and differentiating reactivities were not observed.

Complement Fixation Tests↗
PubMed2025

Potential of MRNA vaccines for mpox prevention: current evidence and future directions.

In 2022, the presumption of monkeypox (mpox) to be of limited epidemiology shifted when a global outbreak was announced. Being a member of the Orthopoxvirus genus in the Poxviridae family, it'd been reported in over 82 countries with over 17 000 confirmed cases by July 2022, thus showing its capability for spreading rapidly. As the smallpox vaccine offers 85% cross-immunity against mpox, the outbreak highlighted the attenuation of global immunity against orthopoxviruses after the cessation of vaccination campaigns against smallpox. The mortality of this virus is higher in vulnerable populations such as children, pregnant women, the elderly, and immunosuppressed individuals. With treatment methods being limited to off-label use of antivirals, the need for urgent and efficient preventative measures is emphasized. At present, JYNNEOS (Modified Vaccinia Ankara-Bavarian Nordic), showing favorable safety, and ACAM2000, a live attenuated virus with a high risk of side effects, are two vaccines that are indicated for mpox immunization. However, neither of them has proven full safety, efficacy, and widespread accessibility against mpox. Hence, the use of mRNA vaccines has emerged as a better alternative to traditional vaccinations, as they leverage synthetic messenger RNA to instruct host cells to produce antigens, eliciting both humoral and cellular immune responses. Though they provided rapid scalability, adaptability to emerging viral variants, and an established safety profile after the COVID-19 pandemic, their usage in preventing mpox remains an area of research. This paper elucidates the potential of mRNA technology to address the unmet needs in mpox prevention. It also highlights the need for genomic surveillance, immunological insights, and innovative delivery systems.

COVID-19↗
PubMed2026

Integrated molecular, epidemiological, and bioinformatics perspectives on the Mpox virus: Implications for surveillance and Global Health preparedness.

Mpox has re-emerged as a significant global zoonotic threat, driven mainly by two large waves the 2022 worldwide Clade IIb outbreak and the 2024 Clade Ib epidemic in Central Africa. This review examines the challenges of interpreting this evolving virus from molecular, epidemiological, and bioinformatics perspectives, with a focus on global health workforce preparedness. Clade IIb largely moved through sexual transmission across countries, but Clade Ib has appeared in a wider population-women, children, and individuals infected through household spread without any sexual contact. Early case series suggest that Clade Ib may cause a more severe disease burden, but more research is needed to directly compare severity and fatality rates with Clade IIb due to the limited number of current studies. The review examines the virus's strategies for evading the host's immune defenses throughout its ∼197 kbp genome, including how it disrupts interferon signaling and creates decoy receptors. This review summarizes the clinical findings of PALM007 and STOMP, noting that neither trial achieved its main efficacy endpoint making routine tecovirimat use less compelling-while leaving open whether it helps particular high-risk groups. A further point is that immunity from the MVA-BN vaccine wanes with time, leading to the growing adoption of booster vaccinations. In conclusion, the review calls for a One Health approach pairing genomic tracking with ecological intelligence and including wastewater surveillance to fill existing gaps in knowledge and enhance the global handling of new orthopoxvirus threats.

Animals↗
PubMed2006

Recognition of vaccinia virus-infected cells by human natural killer cells depends on natural cytotoxicity receptors.

Natural Killer (NK) cells are important in the immune response to a number of viruses; however, the mechanisms used by NK cells to discriminate between healthy and virus-infected cells are only beginning to be understood. Infection with vaccinia virus provokes a marked increase in the susceptibility of target cells to lysis by NK cells, and we show that recognition of the changes in the target cell induced by vaccinia virus infection depends on the natural cytotoxicity receptors NKp30, NKp44, and NKp46. Vaccinia virus infection does not induce expression of ligands for the activating NKG2D receptor, nor does downregulation of major histocompatibility complex class I molecules appear to be of critical importance for altered target cell susceptibility to NK cell lysis. The increased susceptibility to lysis by NK cells triggered upon poxvirus infection depends on a viral gene, or genes, transcribed early in the viral life cycle and present in multiple distinct orthopoxviruses. The more general implications of these data for the processes of innate immune recognition are discussed.

Cell Line↗
PubMed1979

Physical characterization of a stomatitis papulosa virus genome: a cleavage map for the restriction endonucleases HindIII and EcoRI.

The genome of stomatitis papulosa virus (a parapoxvirus) was cleaved with the restriction endonucleases HindIII and EcoRI, each giving rise to 6 fragments respectively. Double digestion with both enzymes resulted in 8 bands, two of which contained DNA fragments in double molar concentrations as revealed by reciprocal digests of isolated DNA fragments. The genome size, estimated by summation of the molecular weights of the fragments, is approximately 86 X 10(6) daltons, some 30 X 10(6) daltons smaller than vaccinia virus (an orthopoxvirus) DNA. The cleavage sites of HindIII and EcoRI endonucleases were mapped on the genome by analysis of reciprocal digests of isolated DNA fragments and by cross-hybridization experiments. This yielded two mapped segments which were then oriented relative to one another by cleavage of isolated partial digestion products. The terminal restriction fragments show rapid renaturation after alkali denaturation and subsequent neutralization, indicating that stomatitis papulosa virus DNA contains terminal cross-links analogous to those found in vaccinia virus DNA.

Animals↗
PubMed2025

Genomic epidemiology of clade Ia monkeypox viruses circulating in the Central African Republic in 2022-24: a retrospective cross-sectional study.

BACKGROUND: The spread of monkeypox virus (Orthopoxvirus monkeypox) clade Ib from the Democratic Republic of the Congo to neighbouring countries has raised global concerns, leading to WHO declaring mpox a public health emergency on Aug 14, 2024. We applied genomic epidemiology to investigate the causes of recurrent mpox outbreaks in the Central African Republic. We aimed to determine whether frequent zoonotic spillovers or increased human-to-human transmissions are driving mpox epidemiology. METHODS: We performed a retrospective cross-sectional study of monkeypox virus genomic sequences among PCR-confirmed mpox cases detected in the Central African Republic between Feb 17, 2022, and Sept 17, 2024. We used hybridisation capture coupled to high throughput sequencing to analyse 46 samples from mpox outbreaks that occurred in eight of the 20 prefectures (14 of 35 health districts). Near-complete genomes were used for phylogenomic analyses. FINDINGS: Between Jan 10, 2022, and Sept 15, 2024, 89 mpox cases were confirmed, including 53 cases in the first 9 months of 2024. We generated 41 near-complete genomes from this period, including 33 from 2024. All new and already published monkeypox virus genomes from the Central African Republic belonged to clade Ia. These genomes spanned the phylogenetic diversity of clade Ia viruses, and most likely represented several dozen independent transmission events to humans. The monkeypox virus phylogenetic diversity was geographically structured within the country. Plausibly linked cases often showed indistinguishable genomes. Conversely, we detected identical genomes in cases that epidemiological information would suggest were independent outbreaks. Finally, we found that three distinct viruses caused cases in the capital city of Bangui in July, 2024, with all three detected on the same day (July 24, 2024). We did not detect substantial enrichment of APOBEC3 editing, suggesting limited human-to-human transmission. INTERPRETATION: The data indicate that mpox epidemiology in the Central African Republic is primarily driven by short-lived outbreaks resulting from many independent zoonotic spillover events, particularly in rural areas. Although evidence remains limited, in Bangui additional factors such as movement of people and importation of bushmeat from other regions might be introducing the virus into urban settings. Similar spillover patterns have been observed in the Democratic Republic of the Congo. The poorly understood nature of monkeypox virus reservoirs in both countries is a regional concern, as frequent spillovers increase the risk of outbreaks leading to sustained human transmission. Beyond strengthening surveillance and developing countermeasures, it is important to better understand the reservoirs and focus on reducing transmission opportunities to prevent further outbreaks. FUNDING: Pasteur Institute of Bangui, Africa CDC, AFROSCREEN, WHO, the Helmholtz Institute for One Health, and the Deutsche Forschungsgemeinschaft.

Humans↗
PubMed1979

Isolation, identification and characterization of camelpox virus in Iraq.

A virus was isolated from pox-like lesions in camels during an outbreak of camelpox disease which occurred in December 1977 in an area near the Iraqi-Iranian border. It was identified serologically as a virus of the Orthopoxvirus group. The biological properties of the isolate indicated that it was probably identical with strains of camelpox virus isolated from Iran, Egypt, Kenya and the U.S.S.R.

Animals↗
PubMed2026

Insights into the Life Cycle and Therapeutic Agents for Monkeypox Virus Infection.

Since the first confirmed case in 1970, the monkeypox virus (MPXV) has emerged as a significant threat to global public health. The World Health Organization (WHO) has declared it a Public Health Emergency of International Concern (PHEIC) on two occasions. Despite decades of research, only tecovirimat has been approved by the European Medicines Agency (EMA) for the treatment of MPXV infection. The genome and structure are similar between MPXV and other orthopoxviruses (OPXVs), suggesting that the strategies used for other OPXVs may be applicable to MPXV. This review systematically summarizes the genome, structure, and critical stages in the life cycle of OPXVs, especially MPXV. A variety of antiviral agents against MPXV and other OPXVs are discussed according to their distinct mechanisms of action: 1) blocking viral entry and fusion, 2) inhibiting DNA replication and processing, 3) disrupting transcription and mRNA processing, 4) preventing virion assembly, maturation and release, 5) modulating immune responses, and 6) mechanism unknown. Overall, this article provides a systematic review of current research progress on potential therapeutic targets and agent for MPXV, aiming to offer innovative insights and strategies for the development of effective therapeutic agents against mpox.

Animals↗
PubMed1979

Serologically cross-reactive polypeptides in vaccinia, cowpox and Shope fibroma viruses.

An immunoprecipitation method coupled with SDS-polyacrylamide gel electrophoresis (SDS-PAGE) was used to identify the serologically cross-reactive polypeptides in Orthopoxvirus (vaccinia and cowpox viruses) and Leporipoxvirus (Shope fibroma virus). Two early and four late polypeptides in cells infected with vaccinia or cowpox virus were specifically immunoprecipitated with antiserum against Shope fibroma virus. Two early and two late polypeptides in cells infected with Shope fibroma virus cross-reacted with both antiserum against vaccinia virus and antiserum against cowpox virus. The possibility of the common polypeptides being related to nucleoprotein antigen in these cross-reactive polypeptides was discussed.

Antigens, Viral↗