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Monkeypox virus as a source of whitepox viruses.

Monkeypox virus cloning and isolation of the so-called 'white' clones from white pocks which this virus forms on the chorioallantoic membrane (CAM) were carried out. The isolated clones were stable and differed considerably from the parental strain. By their properties, they were identical to whitepox viruses formerly isolated from wildlife monkeys and rodents in Equatorial Africa. Besides stable 'white' clones, a number of virus cultures in the process of cloning were obtained which differed in quantitative content of virions, forming on CAM white pocks and pocks with hemorrhages. It appeared that the properties of the viral population as a whole (reaction type on rabbit skin, hemagglutination activity, etc.) depended on the rate of virions produced with different characteristics.

Animals

A comprehensive overview of monkeypox virus disease.

BACKGROUND: Monkeypox (mpox), caused by monkeypox virus (MPXV), re-emerged as a major global public health concern in 2022, resulting in widespread transmission beyond traditionally endemic regions. As of March 2026, 181,164 confirmed cases and 492 deaths had been reported across 144 countries globally. The unprecedented geographic spread of the outbreak highlighted important knowledge gaps in disease surveillance, prevention, and control. Given the ongoing global circulation of MPXV and the risk of future outbreaks, this review provides a comprehensive synthesis of current evidence on MPXV and mpox. METHODS: The literature, surveillance data, and public health reports available up to March 2026 were systematically reviewed and synthesized. The review comprehensively assesses viral biology, genetic diversity, epidemiology, transmission dynamics, clinical manifestations, pathogenesis, laboratory diagnosis, infection during pregnancy, host immune responses, immune evasion mechanisms, therapeutic interventions, and prevention strategies. FINDINGS AND CONCLUSIONS: Globally, the decline in public immunity following the cessation of routine smallpox vaccination, together with ongoing viral evolution, may have contributed to the resurgence of mpox. Advances in genomic surveillance, diagnostics, and public health preparedness have strengthened outbreak response; however, important gaps remain in understanding long-term immunity and optimal treatment strategies. This review summarizes current evidence on MPXV and mpox and highlights priorities for future research and public health interventions.

Antiviral therapy

Differential inhibitory effects of 5-bromodeoxyuridine on vaccinia and monkeypox viruses.

Replication of vaccinia and monkeypox viruses was impeded in the presence of 5-bromodeoxyuridine (BUdR) in RL-33 cells derived from rabbit lung tissue. The different degree of inhibition was found among strains of those viruses, in which it was evident that five strains (CV-1, Lister, IHD, Dairen-I and Ikeda) of vaccinia viruses resulted in more reduced yields of infectious virus than four strains (Sen-19, Orang Utan, Copenhagen and Sierra Leone) of monkeypox viruses. There was also strain variation in BUdR sensitivity within vaccinia viruses but not in the case of monkeypox viruses.

Bromodeoxyuridine

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

Susceptibility of some rodent species to monkeypox virus, and course of the infection.

The authors studied the susceptibility of five species of rodent to monkeypox virus inoculated by various routes and the course of the infection. Reactions varied from complete resistance to lethal generalized infection with rash. Rabbits and white mice appeared to be the most susceptible species and young animals were more susceptible than adults. Monkeypox virus was found to infect young animals by natural routes, i.e., per os and intranasally. Transmission by contact occurred among 10-day-old rabbits. Since antibodies to monkeypox virus may persist for over a year in the sera of convalescent animals, serological examination of animals is recommended for studying the ecology of this virus.

Animals

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

Structure and operating principles of a monkeypox virus replisome.

Poxviruses are double-stranded DNA viruses with large genomes. Among them, monkeypox virus (MPXV) has been responsible for two recent public health emergencies as declared by the World Health Organization1. The MPXV polymerase comprises three subunits-a catalytic subunit (F8) and a heterodimeric processivity factor (A22 and E4). The viral polymerase must coordinate activities with the hexameric helicase-primase (E5) to initiate replication of the viral genome2. Although structures of MPXV E5 (refs. 3,4) and the polymerase5-7 in isolation are available, how they assemble into a functional replisome remains unclear. In isolation, E5 is in an autoinhibited conformation and has very weak helicase activity3,4, and the mechanism for helicase activation is unclear. Here we used cryo-electron microscopy to determine the structures of DNA-bound MPXV replisomes comprising the polymerase holoenzyme (F8, A22 and E4) and the E5 helicase hexamer. We show that, during replisome assembly, E5 undergoes large-scale conformational changes that allow two of its primase domains to interact with the polymerase F8 thumb and A22 subunit. Biochemical assays and single-molecule experiments reveal that this E5 conformational change is coupled to helicase activation and enhances primase activity. Taken together, these findings identify fundamental mechanisms governing coordinated helicase and polymerase activities during DNA replication for an important class of viral pathogens.

Journal Article

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

[Use of the monkey pox virus for evaluating the intensity of the immunity against smallpox in experiments on M. rhesus].

Monkeypox virus causing in M, rhesus upon aerogenic infection a disease similar to human varioloid was used to evaluate the intensity of immunity against smallpox in immunized M. rhesus monkeys. Postvaccination immunity was solid in all the animals vaccinated intradermally or orally. In 2 out of 14 monkeys immunized orally, however, the immunity was partially overcome. Neutralizing antibody titers in these two monkeys were 1:5 and 1:25, respectively. This agreed with the observations made in Pakistan indicating the possibility that some humans having serum neutralizing antibody titers up to 1:32 could contract smallpox and develop the disease.

Animals

The virion and soluble antigen proteins of variola, monkeypox, and vaccinia viruses.

The structural proteins in purified preparations of variola, monkeypox, and vaccinia viruses were separated and compared by using a high resolution SDS-polyacrylamide gel electrophoresis system. About 30 proteins were resolved for each virus by autoradiography of longitudinally-sliced gel rods. Although the autoradioelectropherograms of each virus were similar, it was possible to differentiate them by their unique protein pattern in the 30,000 to 40,000 molecular weight region of the gels. A single virion glycoprotein (mol. wt. = 38 X 10(3)) and a virion phosphoprotein (mol. wt. = 12 X 10(3)) were associated with each of the virus preparations. Cross-absorbed monospecific immune sera against variola, monkeypox, and vaccinia virus-infected cells were used in immunodiffusion tests to precipitate radiolabeled, homologous, soluble antigen proteins. The predominant antigen protein associated with each immunospecific precipitate had a molecular weight of approximately 73,000.

Antigens, Viral

Monkeypox and whitepox viruses in West and Central Africa.

Prospects for the eradication of smallpox are now highly encouraging. With the cessation of man-to-man transmission, the question of possible animal reservoirs of smallpox becomes increasingly important. During the period 1970-1975, 20 cases of a smallpox-like disease were detected in smallpox-free areas of tropical rain forest in West and Central Africa. Epidemiological and virological investigations revealed that the disease was caused by an animal poxvirus termed monkeypox virus, a member of the orthopox virus group. The disease spread with difficulty even among susceptible close contacts and does not appear to be sufficiently transmissible to permit continuing infection to become established in man. During the investigations, four orthopox viruses termed whitepox viruses were isolated from rodents and monkeys. The isolates were not distinguishable from variola virus with currently available laboratory techniques, but there is no evidence so far that viruses of this group have infected man. Although there is now substantial and accumulating evidence that there is no animal reservoir for smallpox, continued surveillance and studies in West and Central Africa are warranted.

Africa, Central

Mpox: current knowledge and understanding-a scoping review.

Mpox in humans is a rash illness resulting from infection with monkeypox virus (MPXV). In 2022, a public health emergency of international concern (PHEIC) was declared with 115 countries reporting cases of Mpox. Most of these countries had not previously reported cases. This global outbreak was sustained primarily by human-to-human transmission within complex sexual networks. Whilst these cases were similar to previous clade II West African MPXV isolates, they were sufficiently genomically distinct to result in WHO recognizing two subclades within clade II: clade IIa and clade IIb. In 2024, a second PHEIC was declared, resulting from a marked increase in cases of clade I MPXV. In this scoping review, we compare the major clinical, epidemiological, and genomic features of the major mpox lineages and the implications for vaccination, transmission, infection control and treatment..

Humans

Genomic Epidemiology and Clinical Characteristics of Mpox Lineage C.1 Outbreak in Thailand, 2023-2024.

Since 2022, human monkeypox virus (hMPXV) has emerged in non-endemic regions, including Thailand. However, the genomic dynamics and clinical correlates of local transmission remain incompletely defined. Whole-genome sequencing was performed on hMPXV from 16 patients in Thailand (2023-2024) using targeted amplicon NGS. Phylogenetic analyses integrated global reference sequences. Mutational profiles, specifically non-synonymous substitutions and APOBEC3-associated signatures, were analyzed in relation to clinical data. Phylogenetic reconstruction identified three temporal phases. Early 2022 cases (clade IIb lineages A and B) were interspersed with global sequences, consistent with multiple introductions. In contrast, 2023-2024 cases were dominated by lineage C.1. All 16 genomes belonged to C.1 (one C.1.1), and formed a distinct mid-2023 cluster, designated C.1/Thai/Cluster, supporting sustained local transmission. APOBEC3-associated mutations were pervasive across the C.1 lineage overall, including within C.1/Thai/Cluster, without evidence of significant enrichment specific to this cluster. The cohort comprised exclusively male patients (81% HIV-positive, MSM), with predominantly genital painful lesions and a median recovery time of 23 days. No significant associations were detected between viral genetic variation and clinical outcomes. Mpox transmission in Thailand evolved from multiple introductions to sustained C.1-dominated local spread, underscoring the importance of continued genomic surveillance.

Humans

[Generalized monkeypox in orally infected rabbits and white mice].

In the past 5 years 17 human cases of monkeypox with 4 deaths were reported in African countries. The source and the mechanism of transmission of the infection are unknown. One of the possible modes of human infection could be through monkey meat used for food. The paper presents the results of the study of susceptibility of 4 species of laboratory animals to monkeypox virus given orally. Adult rabbits, guinea pigs, and hamsters were found to be resistant. Ten-day-old rabbits and 8-, 10- and 12-day-old mice developed generalized infection with eruptions and high lethality. The infection was transmitted to uninfected rabbits of the same litter, apparently by air-borne droplet mode. The obtained model of generalized monkeypox infection after per os administration of the virus and the fact of air-borne droplet transmission of infection may serve as indirect evidence of the possibility of transmission of the infection by this mode in nature.

Animals

Experimental smallpox in chimpanzees.

In an attempt to prepare highly specific antiserum to variola virus, a chimpanzee was inoculated with a virulent human strain of this virus. Three uninoculated chimpanzees were housed in the same room; two of these developed clinical disease with seroconversion, while the third developed no evidence of infection and no antibody. The three animals that became ill also developed antibody to vaccinia and monkeypox viruses. Human contacts during the study and following a break in containment showed no evidence of infection as determined by serological tests and lack of clinical disease.

Animals