Lumpy Skin Disease Research Articles

A Real-Time Recombinase Polymerase Amplification Assay for Specific Detection of Lumpy Skin Disease Virus.

Lumpy skin disease virus (LSDV) infection, accompanied by loss of hide quality, poor reproductive efficiency, consistent degenerative emaciation, and milk yield reduction of animals, causes severe economic implications in endemic zones. The heterologous attenuated goat pox (GTPV) vaccine (AV41 strain) was used in China to prevent LSDV infection. Only a few LSDV detection methods that distinguish LSDV from GTPV vaccine strains have been reported before. For simple, rapid, and specific detection of LSDV, the real-time recombinase polymerase amplification (RPA) method was established with the specific primers and probes designed according to the conserved regions of ORF132 gene sequences. The assay could be finished within 20 min at a constant temperature (39 °C). This method had a limit of detection (LOD) of 15 copies/μL for LSDV and no cross-reaction with the nucleic acids of goat pox virus, infectious bovine rhinotracheitis virus, Pasteurella multocida, and bovine healthy tissue. Furthermore, 43 clinical samples were detected by this method and the real-time PCR recommended by the World Organisation for Animal Health (WOAH), with a kappa value, was 0.94. These results demonstrated that the real-time RPA method for detecting LSDV developed in this study was characterized by high sensitivity and specificity, which has wide application value in the clinical diagnosis and detection of LSDV in China.

OPTIMIZATION OF THE MAIN PARAMETERS OF A LATERAL FLOW ASSAY BASED ON THE RECOMBINANT Р32 ANTIGEN OF LUMPY SKIN DISEASE VIRUS

Lumpy skin disease is a highly contagious infectious transboundary disease of cattle, resulting in significant economic losses. The wide and rapid spread of lumpy skin disease to new territories emphasizes the objective need to improve diagnostic methods. The article outlines the findings of lateral flow assay parameter optimization for lumpy skin disease detection using recombinant P32 antigen. It was found that the optimal amount of protein for immobilization on 20 nm colloidal gold particles was 20 µg/mL. Bovine serum albumin at a final concentration of 0.25% was used to stabilize the conjugate. The optimal dilution of the conjugate was 1:2, and the concentration of recombinant protein and anti-species antibodies for application to the membrane was 500 μg/ml and 250 μg/ml, respectively. The colloidal gold conjugate interacted with antibodies and specifically reacted with the recombinant protein. No cross-reaction with other proteins was noticed at the same time. The created express test allowed for the detection of antibodies from immunized animals when the serum was diluted up to 1:200, however, 1:50 was the ideal ratio. The conjugate remained active after 90 days of storage at room temperature. The findings demonstrate the express method's potential for use in serological research for the prevention and control of the spread of lumpy skin disease.

Molecular and Epidemiological Analyses of Sheeppox Outbreaks in Russia from 2013 to 2021

Sheeppox (SPP) is a transboundary infectious disease that affects sheep and goats, leading to significant losses in countries with extensive small ruminant breeding programs. While sporadic SPP outbreaks have been observed in the Russian Northern Caucasus and the Far East, the number of SPP outbreaks in the Russian Central and Far East regions has increased recently. However, there is a lack of epidemiological data on SPP virus (SPPV) in the Northern latitudes. In this study, we conducted epidemiological and genetic analyses of SPP outbreaks in Russia from 2013 to 2021 using whole-genome sequences of five selected isolates. The epidemiological data revealed an elevated risk of SPP outbreaks during the summer months, although outbreaks were not limited to this period. A phylogenetic analysis of the whole-genome sequences of selected SPPVs obtained directly from clinical samples revealed a unique cluster of SPPV isolates circulating in Central Russia, which was related to previous isolates from the European part of Russia. In contrast, SPPVs obtained from the Russian Far East showed genetic similarity to isolates detected in Southeast Asia. The whole-genome sequences demonstrated that the reported outbreaks were not related to the NISKHI vaccine strain, which was used to combat lumpy skin disease and SPP in Russia. Based on the study findings and GenBank data, we propose a novel cluster designation system for SPPV genomic sequences.

Field-friendly and ultra-fast detection platform without nucleic acid extraction for virus detection

The polymeric chain reaction (PCR) has come under fire for being time-consuming, requiring expensive equipments, and requiring the extraction and purification of nucleic acids. Here, an ultra-fast and sensitive detection platform without nucleic acid extraction solved the above problems. Firstly, the RoomTemp Sample Lysis Kit released the nucleic acid in 3 min and removed the inhibition to facilitate the amplification reaction. What's more, ultra-fast PCR (UF-PCR) can complete 40 cycles in just 15 min and 50 s. To improve the sensitivity and provide more convenient reading modes, CRISPR/Cas12a was mediated to detect Lumpy skin disease virus (LSDV). The platform output fluorescence and Lateral flow dipstick (LFD) signals. The actual detection limit was 2 × 101 copies·μL−1. The portable platform realized visualization, excellent sensitivity and quick speed. In summary, the field-friendly testing platform had great potential in practical testing.

Tingkat Pengetahuan Panitia Kurban Tentang Penyakit Lumpy Skin Disease di Kota Bandar Lampung

Lumpy Skin Disease (LSD) is transboundary disease and characterized by the presence of nodules on the skin This Study is aimed to assess the level of knowledge of the sacrificial committee towards Lumpy Skin Disease (LSD) in Bandar Lampung City. The data were taken by using research instruments (questionnaire) with 100 respondents. The Research subjects in this study were sacrificial committees in 20 districts around Bandar Lampung City. Sacrificial committees were dominated by 50-60 years old, level of education Senior High School, and 1-10 years experienced in becoming sacrificial committee. Results showed that the average level of respondents’ knowledge regarding the LSD symptoms is high (80), whereas the knowledge towards LSD transmission, and control are in the medium level (72.06 and 64.3)

Development of a Real-Time qPCR Method for the Clinical Sample Detection of Capripox Virus.

Capripox viruses (CaPVs), including sheep pox virus (SPV), goat pox virus (GPV), and lumpy skin disease virus (LSDV), are the cause of sheep pox (SPP), goat pox (GTP), and lumpy skin disease (LSD) in cattle. These diseases are of great economic significance to farmers, as they are endemic on farms and are a major constraint to international trade in livestock and their products. Capripoxvirus (CaPV) infections produce similar symptoms in sheep and goats, and the three viruses cannot be distinguished serologically. In this study, we developed a real-time quantitative polymerase chain reaction (qPCR) method for identifying CaPV in goats, sheep, and cattle. Clinical samples were tested and verified. The developed assay was highly specific for target viruses, including GPVSPV and LSDV, which had no cross-reaction with other viruses causing similar clinical symptoms. An artificially synthesized positive control plasmid using the CaPV 32 gene inserted into the vector pMD19-T was used as a template, and the correlation coefficient of the linear regression curve (R2) was 0.9916, the estimated amplification efficiency (E) was 96.06%, and the sensitivity (limit of detection, LOD) was 3.80 copies per reaction. Using the clinical samples as a template, the limit of detection (LOD) was 4.91 × 10-5 ng per reaction (1.60 × 10-5-2.13 × 10-3 ng, 95% confidence interval (CI)), which means that this method was one of the most sensitive detection assays for CaPVs. A total of 85 clinical samples from CaPV-infected animals (goats, sheep, and cattle) and 50 clinical samples from healthy animals were used to test and compare the diagnostic results using the Synergy Brands (SYBR) Green-based PCR method recommended by the World Organization of Animal Health (WOAH). Both diagnostic sensitivity (DSe) (95.8-100%, 95% CI) and diagnostic specificity (DSp) (92.9-100%, 95% CI) results of the real-time quantitative PCR (qPCR) and SYBR Green PCR were 100%, and the kappa value (κ) was 1.0 (1-1, 95% CI). In summary, the assay established based on TaqMan probes was advantageous in high specificity, sensitivity, and general applicability and could be a competitive candidate tool for the diagnosis of CaPV in clinically suspected animals.

Risk factors, logistic model, and vulnerability mapping of lumpy skin disease in livestock at the farm level in Indragiri Hulu District, Riau Province, Indonesia, in 2022.

Lumpy skin disease (LSD) is an emerging epidemic in livestock in Indonesia. It was first reported in the Indragiri Hulu Regency of Riau Province, which has more cases than the surrounding regencies. This study aimed to identify the risk factors and generate a logistic regression model and vulnerability map of LSD in the Indragiri Hulu Regency. We used a structured questionnaire to interview the case and control farm owners to evaluate the risk factors. We evaluated 244 samples, consisting of 122 case and control farm samples each. At the cattle farm level, the risk factor data related to LSD were analyzed using descriptive statistics, bivariate analysis with Chi-square, and odds ratio, while the logistic model was derived using multivariate logistic regression analysis. Using variables, such as the number of cases and risk factor variables included in the model logistic, and the temperature, humidity, and rainfall data from the Meteorology, Climatology, and Geophysical Agency, we analyzed the vulnerability map of LSD in the regency using scoring, weighting, and overlay methods. Ten significant risk factors were associated with LSD occurrence. The LSD model obtained from the logistic regression analysis was LSD (Y) = -3.92095 + 1.13107 (number of cattle >3) + 1.50070 (grazing cattle together with other farmers' cattle) + 1.03500 (poor management of farm waste/dirt) + 2.49242 (presence of livestock collectors/traders near the farm location) + 1.40543 (introduction of new livestock) + 2.15196 (lack of vector control measures on the farm). The LSD vulnerability map indicated that the villages with high vulnerability levels were Rantau Bakung, Kuantan Babu, and Sungai Lala in the Rengat Barat, Rengat, and Sungai Lala subdistricts, respectively. We found 10 significant risk factors associated with LSD occurrence. The LSD model included the number of cattle (>3), cograzing with other farmers' cattle, poor management of farm waste/dirt, the presence of livestock collectors/traders near the farm, introduction of new livestock, and lack of vector control measures on the farm. The LSD vulnerability map indicated that villages with high vulnerability levels included Rantau Bakung in the Rengat Barat subdistrict, Kuantan Babu in the Rengat subdistrict, and Sungai Lala in the Sungai Lala subdistrict.

Molecular detection, Isolation and characterization of lumpy skin disease virus in Andhra Pradesh, India

Molecular detection, Isolation and characterization of lumpy skin disease virus in Andhra Pradesh, India

Development and application of a real-time polymerase chain reaction assay to detect lumpy skin disease virus belonging to the Kenyan sheep and goat pox group

Lumpy skin disease (LSD) outbreaks in Southeast and South Asia are attributed to different lineages of LSD virus (LSDV). Variants belonging to the novel recombinant cluster 2.5 circulate in China and Thailand, while a Kenyan sheep and goat pox (KSGP) strain from cluster 1.1 circulates in India, Pakistan, and Bangladesh. The clusters representing these circulating strains are vastly different. However, if their distribution encroaches into each other’s ranges, it will be impossible to differentiate between them due to the lack of suitable molecular tools. Thus, fit-for-purpose molecular tools are in demand to effectively and timeously diagnose and investigate the epidemiology of LSDVs in a region. These could significantly contribute to the phylogenetic delineation of LSDVs and the development of preventive measures against transboundary spillovers. This work aimed to develop a real-time polymerase chain reaction assay targeting open reading frame LW032, capable of specifically detecting KSGP-related isolates and recombinant LSDV strains containing the KSGP backbone. The analytical specificity was proven against the widest possible panel of recombinant vaccine-like LSDV strains known to date. The amplification efficiency was 91.08%, and the assay repeatability had a cycle threshold variation of 0.56–1.1 over five repetitions across three runs. This KSGP-specific assay is reliable and fast and is recommended for use in LSDV epidemiological studies where the accurate detection of KSGP genetic signatures is a priority, particularly in regions where KSGP-like and other lineages are circulating.

An Exemplary Computational Approach to Investigate Lumpy Skin Disease in Indian Cattle

Lumpy Skin Disease (LSD) is a highly consequential infectious ailment that affects cattle caused by the Lumpy Skin Disease Virus (LSDV), which is a DNA virus classified under the Capripoxvirus genus of the Poxviridae family. This affliction presents a significant obstacle in the cattle industries of several Asian and African countries. Although the virus may be found in many physiological fluids and excretions, such as sperm, skin lesions are the primary source of infection. Hematophagous arthropods, such as biting flies, mosquitoes, and ticks, act as mechanical vectors for transmission. The geographical expansion of LSDV is believed to have been assisted by vector-borne transmission. However, a lack of quantitative understanding of the transmission of LSDV hinders the implementation of efficient disease control measures. Obstacles as mentioned earlier, this work focuses on developing a mathematical model to analyze the phenomenon of Lumpy Skin Disease, with a specific emphasis on its implications for the cattle sectors in African and Asian countries. The model encompasses a set of differential equations incorporating the influences of infection forces originating from sick and asymptomatic cattle, along with infected vectors. The research demonstrates a plausible correlation between Lumpy Skin Disease and increased death rates in cattle. Employing rigorous examination and computational modelling, a valuable understanding of the fundamental dynamics of disease outbreaks is obtained. The mathematical model shows potential for predicting the future transmission of Lumpy Skin Disease. This presents a prospective opportunity for understanding and alleviating the disease's effects on bovine populations. Moreover, the analysis reveals that the impact of direct contact transmission on the spread of LSDV during documented outbreaks was negligible, therefore providing valuable insights into the dynamics of disease transmission. As the model is rigorously analyzed to gain insights into its qualitative dynamics of epidemics, which are present in the numerical simulations, this mathematical model can be allowed to estimate the future spread of the disease.

Potential Benefits of Propolis in Large and Small Animal Practices: A Narrative Review of the Literature

Propolis is a resinous substance from a mixture of different plant parts and molecules bees compose. This narrative review article explored the application of propolis in large and small animal practices in PubMed, Scopus, and Google Scholar databases. Propolis is applied in different pharmaceutical forms. Due to its numerous biological actions, such as antimicrobial, anti-inflammatory, antioxidant, antiparasitic, antiulcer, antitumor, and immunomodulatory, propolis can improve animal health and production. Propolis could be used as an alternative treatment for many diseases, such as mastitis, lumpy skin disease, foot and mouth disease, reproductive disorders, and diarrhea in cattle. Moreover, it could improve weight gain in cattle. In equine, propolis has been used as a local anesthetic and for treating dermatomycosis, chronic bronchitis, and skin wounds. In pigs, propolis has been used to treat enzootic pneumonia and as a prophylaxis for gastrointestinal and respiratory diseases in weak pigs. Propolis has been applied to treat caseous lymphadenitis and parasitic diseases in sheep and goats. Furthermore, it improves the immune status of kids and the health status of late pregnant ewes. In dogs and cats, propolis has been applied to treat otitis externa, eye diseases, Cushing’s syndrome, and dermatophytosis. In dogs, propolis can treat transmissible venereal tumors. Moreover, propolis positively affects animal production, average daily gain and milk yield in sheep, growth of calves, lambs, and piglets, and cow’s milk nutritional quality. On the other hand, the addition of propolis to the diet of feedlot bulls and pigs has no effect on their feed intake, hematological, biochemical, and immunological parameters, nutrient digestibility, microbial synthesis, and carcass characteristics. Based on the available clinical studies, propolis has potential benefits for animal health in cattle, equine, sheep, goats, pigs, dogs, and cats. According to the available literature, propolis is a natural promising agent that can alternate conventional pharmaceuticals, particularly antibiotics. It improves animal health and production with no adverse effects and low cost. Most conducted studies on the efficacy of propolis on animal health and production are in vitro. Due to its scarcity, further controlled clinical trials are recommended to evaluate the exact usefulness of propolis in veterinary medicine and to obtain reliable conclusions on the benefits of propolis in animal health and production.

Constitutive proteins of lumpy skin disease virion assessed by next-generation proteomics.

Lumpy skin disease virus (LSDV) is the causative agent of an economically important cattle disease which is notifiable to the World Organisation for Animal Health. Over the past decades, the disease has spread at an alarming rate throughout the African continent, the Middle East, Eastern Europe, the Russian Federation, and many Asian countries. While multiple LDSV whole genomes have made further genetic comparative analyses possible, knowledge on the protein composition of the LSDV particle remains lacking. This study provides for the first time a comprehensive proteomic analysis of an infectious LSDV particle, prompting new efforts toward further proteomic LSDV strain characterization. Furthermore, this first incursion within the capripoxvirus proteome represents one of very few proteomic studies beyond the sole Orthopoxvirus genus, for which most of the proteomics studies have been performed. Providing new information about other chordopoxviruses may contribute to shedding new light on protein composition within the Poxviridae family.

Examination of critical factors influencing ruminant disease dynamics in the Black Sea Basin.

Ruminant production in the Black Sea basin (BSB) is critical for national economies and the subsistence of rural populations. Yet, zoonoses and transboundary animal diseases (TADs) are limiting and threatening the sector. To gain a more comprehensive understanding, this study characterizes key aspects of the ruminant sector in nine countries of the BSB, including Armenia, Azerbaijan, Belarus, Bulgaria, Georgia, Moldova, Romania, Türkiye, and Ukraine. We selected six priority ruminant diseases (anthrax, brucellosis, Crimean Congo haemorrhagic fever (CCHF), foot-and-mouth disease (FMD), lumpy skin disease (LSD), and peste des petits ruminants (PPR)) that are present or threaten to emerge in the region. Standardized questionnaires were completed by a network of focal points and supplemented with external sources. We examined country and ruminant-specific data such as demographics, economic importance, and value chains in each country. For disease-specific data, we analysed the sanitary status, management strategies, and temporal trends of the selected diseases. The shift from a centrally planned to a market economy, following the collapse of the Soviet Union, restructured the ruminant sector. This sector played a critical role in rural livelihoods within the BSB. Yet, it faced significant challenges such as the low sustainability of pastoralism, technological limitations, and unregistered farms. Additionally, ruminant health was hindered by informal animal trade as a result of economic factors, insufficient support for the development of formal trade, and socio-cultural drivers. In the Caucasus and Türkiye, where diseases were present, improvements to ruminant health were driven by access to trading opportunities. Conversely, European countries, mostly disease-free, prioritized preventing disease incursion to avoid a high economic burden. While international initiatives for disease management are underway in the BSB, there is still a need for more effective local resource allocation and international partnerships to strengthen veterinary health capacity, protect animal health and improve ruminant production.

Production of recombinant lumpy skin disease virus A27L and L1R proteins for application in diagnostics and vaccine development

Vaccination using live attenuated vaccines (LAVs) is considered the most effective method for control of lumpy skin disease (LSD). However, this method is limited by safety concerns, with reports of adverse reactions following vaccination. This study evaluates A27L and L1R which are essential proteins for virus attachment and membrane fusion as recombinant sub-unit vaccines against LSD. These proteins were recombinantly expressed in Escherichia coli and purified using affinity chromatography. Purified proteins were formulated individually (A27L or L1R) and in combination (A27L and L1R) with 10% (w/w) Montanide™ Gel 01 PR adjuvant at a final antigen dose of 20 µg per protein. The safety and immunogenicity of these formulations were evaluated in rabbits in a 42-day clinical trial. Animals were vaccinated on day 0 and boost injection administered 21 days later. No reduced morbidity, increased temperature and any other clinical signs were recorded in vaccinated animals for all three vaccine formulations. The highest neutralizing antibody response was detected on day 42 post-primary vaccination for all formulations when using serum neutralising assay. The neutralisation data correlates with antibody titres quantified using a whole cell ELISA. Evaluating the combination of A27L and L1R as potential diagnostic reagents showed highest sensitivity for detection of antibodies against LSD when compared to individual proteins. This study reports the immunogenicity of recombinant A27L and L1R combination for successful application in LSD vaccine development. Furthermore, these proteins demonstrated the potential use in LSD diagnostics.

Comparison of Gross Pathology between Classical and Recombinant Lumpy Skin Disease Viruses.

The pathology caused by three different isolates of lumpy skin disease virus, classical field cluster 1.2 strain Dagestan/2015, recombinant vaccine-like cluster 2.1 strain Saratov/2017, and cluster 2.2 strain Udmurtiya/2019, in cattle was compared from experimental infections. The infection of cattle was performed using intravenous administration of 2 mL of 105 TCID50/mL of each specific LSDV. Both classical and recombinant forms of LSDV cause pathological changes in the skin and lymph nodes, as well as the trachea and lungs. Due to circulatory disorders in the affected organs, multiple areas of tissue necrosis were observed, which, with the resurgence of secondary microflora, led to the development of purulent inflammation. Observed pathological changes caused by the recombinant vaccine-like strain Udmurtiya/2019 were characterized by a more pronounced manifestation of the pathoanatomical picture compared to the classical field strains Dagestan/2015 and Saratov/2017. Interestingly, Dagestan/2015 and Udmurtiya/2019 caused damage to the lymph nodes, characterized by serous inflammation and focal purulent lymphadenitis caused by purulent microflora. "Saratov/2017" did not cause pathology in the lymph nodes. All LSDVs were virulent and caused pathology, which was not distinguishable between viruses. This data set will serve as the experimentally validated basis for the comparative examination of novel LSDV strains in gross pathology.

A quantitative risk assessment for the incursion of lumpy skin disease virus into Australia via long-distance windborne dispersal of arthropod vectors.

Lumpy skin disease (LSD) is an infectious disease of cattle and water buffalo caused by lumpy skin disease virus (LSDV). It is primarily transmitted mechanically by biting insects. LSDV has spread from Africa to the Middle-East, the Balkans, Caucasus, Russia, Kazakhstan, China, Asia and India, suggesting that a wide variety of arthropod vectors are capable of mechanical transmission. In 2022, LSD was detected in Indonesia, heightening awareness for Australia's livestock industries. To better understand the risk of LSDV incursion to Australia we undertook a quantitative risk assessment (QRA) looking at windborne dispersal of arthropod vectors, assuming a hypothetical situation where LSD is endemic in south-east Asia and Papua New Guinea. We estimated the risk of LSDV incursion to be low, with a median incursion rate of one incursion every 403 years, based on a model where several infectious insects (i.e. a 'small batch' of 3-5) must bite a single bovine to transmit infection. The incursion risk increases substantially to one incursion every 7-8 years if a bite from a single insect is sufficient for transmission. The risk becomes negligible (one incursion every 20,706 years) if bites from many insects (i.e. a 'large batch' of 30-50 insects) are necessary. Critically, several of our parameter estimates were highly uncertain during sensitivity analyses. Thus, a key outcome of this QRA was to better prioritise surveillance activities and to understand the key research gaps associated with LSDV in the Australasian context. The current literature shows that multiple vectors are required for successful bovine-to-vector transmission of LSDV, suggesting that our estimate of one outbreak every 403 years more accurately represents the risk to Australia; however, the role of single insects in transmission has not yet been evaluated. Similarly, attempts to transmit LSDV between bovines by Culicoides have not been successful, although midges were the highest risk vector category in our model due to the high vector-to-host ratio for midges compared to other vector categories. Our findings provide further insight into the risk of LSD to Australian cattle industries and identify the Tiwi Islands and areas east of Darwin as priority regions for LSDV surveillance, especially between December and March.

Lumpy skin disease: the underestimated epidemic for cattle in India

Lumpy skin disease: the underestimated epidemic for cattle in India

Global Burden of Lumpy Skin Disease, Outbreaks, and Future Challenges.

Lumpy skin disease (LSD), a current global concern, causes economic devastation in livestock industries, with cattle and water buffalo reported to have higher morbidity and lower mortality rates. LSD is caused by lumpy skin disease virus (LSDV), a member of the Poxviridae family. It is an enzootic, rapidly explorative and sometimes fatal infection, characterized by multiple raised nodules on the skin of infected animals. It was first reported in Zambia in 1929 and is considered endemic in Africa south of the Sahara desert. It has gradually spread beyond Africa into the Middle East, with periodic occurrences in Asian and East European countries. Recently, it has been spreading in most Asian countries including far East Asia and threatens incursion to LSD-free countries. Rapid and accurate diagnostic capabilities, virus identification, vaccine development, vector control, regional and international collaborations and effective biosecurity policies are important for the control, prevention, and eradication of LSD infections. This review critically evaluates the global burden of LSD, the chronological historical outbreaks of LSD, and future directions for collaborative global actions.

Seroprevalence of Brucellosis Disease and Lumpy Skin Disease on Cattles at Svay Rieng and Prey Veng Province, Cambodia

Seroprevalence of Brucellosis Disease and Lumpy Skin Disease on Cattles at Svay Rieng and Prey Veng Province, Cambodia

Human FAM111A inhibits vaccinia virus replication by degrading viral protein I3 and is antagonized by poxvirus host range factor SPI-1

Zoonotic poxviruses such as mpox virus (MPXV) continue to threaten public health safety since the eradication of smallpox. Vaccinia virus (VACV), the prototypic poxvirus used as the vaccine strain for smallpox eradication, is the best-characterized member of the poxvirus family. VACV encodes a serine protease inhibitor 1 (SPI-1) conserved in all orthopoxviruses, which has been recognized as a host range factor for modified VACV Ankara (MVA), an approved smallpox vaccine and a promising vaccine vector. FAM111A (family with sequence similarity 111 member A), a nuclear protein that regulates host DNA replication, was shown to restrict the replication of a VACV SPI-1 deletion mutant (VACV-ΔSPI-1) in human cells. Nevertheless, the detailed antiviral mechanisms of FAM111A were unresolved. Here, we show that FAM111A is a potent restriction factor for VACV-ΔSPI-1 and MVA. Deletion of FAM111A rescued the replication of MVA and VACV-ΔSPI-1 and overexpression of FAM111A significantly reduced viral DNA replication and virus titers but did not affect viral early gene expression. The antiviral effect of FAM111A necessitated its trypsin-like protease domain and DNA-binding domain but not the PCNA-interacting motif. We further identified that FAM111A translocated into the cytoplasm upon VACV infection by degrading the nuclear pore complex via its protease activity, interacted with VACV DNA-binding protein I3, and promoted I3 degradation through autophagy. Moreover, SPI-1 from VACV, MPXV, or lumpy skin disease virus was able to antagonize FAM111A by prohibiting its nuclear export. Our findings reveal the detailed mechanism by which FAM111A inhibits VACV and provide explanations for the immune evasive function of VACV SPI-1.