Lumpy skin disease (LSD), caused by the lumpy skin disease virus (LSDV), is a global concern that affects cattle and buffalo. Recently, the disease has been reported in new species such as the Indian Gazelle, Camel, Banteng, Gaur, and Giraffe from various parts of the world. This report provides an insight into the occurrence of LSD in Yak from Sikkim, a North-Eastern state of India. During the investigation, both cattle and yak exhibited typical clinical signs of LSD, including skin nodular lesions. The morbidity, mortality, and case fatality rates for cattle were 9.08%, 1.84%, and 20.24%, respectively. Similarly, the morbidity, mortality, and case fatality rates in yak were 7.57%, 1.24%, and 16.33%, respectively. The virus isolation and amplification of LSDV-specific genes confirmed the presence of LSDV in cattle, yak, and vectors. Further, demonstrated antibodies in randomly collected sera from naïve and unvaccinated cattle and yak using indirect Enzyme Linked Immuno-sorbent Assay (iELISA) and Serum Neutralisation test (SNT) from this region. Sequencing and phylogenetic analysis of P32, GPCR, and RPO30 genes revealed that the virus isolated from both species was 100% identical to each other and also closely related to the field LSDV isolates circulating in the Indian subcontinent. The study highlighted the emergence of LSDV in unconventional hosts and underscored the need to include other bovine species in national disease control programs, encompassing disease surveillance initiatives.

Lumpy skin disease (LSD) is a re-emerging viral transboundary disease affecting cattle and buffaloes, resulting in a significant socio-economic impact on the affected regions. LSD is primarily transmitted among susceptible livestock through hematophagous vectors, including ticks and flies. Ticks also function as reservoirs for various haemoprotozoan parasites, increasing the likelihood of coinfections in affected animals. This study investigates the comorbidity of LSD and associated risk factors using diverse datasets. A total of 414 samples from LSD-suspected animals were screened for LSD, infectious bovine rhinotracheitis (IBR), malignant catarrhal fever (MCF), babesiosis, and theileriosis (Theileria annulata and Theileria orientalis), as well as anaplasmosis. Among these, 214 (51.6%) tested positive for LSD. A strong correlation was identified between LSD and oriental theileriosis caused by Theileria orientalis (50.9%). Other significant associations were observed with IBR (34.1%), anaplasmosis (24.7%), tropical theileriosis (15.4%), babesiosis (12.6%), and MCF (12.1%). The transmission dynamics of LSD revealed that hematophagous vectors, particularly Stomoxys, Haematobia, and Rhipicephalus, play a crucial role in its spread, especially in unorganised farming systems. Additionally, Haematobia and Stomoxys flies were implicated in the high transmission rate of oriental theileriosis (39%) in conjunction with LSD. Notably, ticks (Rhipicephalus) facilitated the concurrent transmission of one, two, or three infections alongside LSD. While Musca, a non-hematophagous fly, was found to carry LSD virus (LSDV), it did not test positive for other pathogens. This study highlights the potential for cattle to harbour multiple diseases simultaneously with LSD, emphasising the necessity for integrated transmission studies and comprehensive disease screening in affected livestock. These findings underscore the importance of implementing targeted prevention and control strategies to mitigate disease impact in livestock populations.

Background: Lumpy skin disease (LSD) is major transboundary disease affecting cattle and water buffaloes, indirectly causing huge socio-economic losses. Following its first outbreak in India in 2019, the heterologous Goatpox (Uttarkashi strain) vaccine mitigated LSD. Objective: Due to limited data on the spatiotemporal distribution of the disease, this study investigates its dynamics and presents findings from a field study conducted in Maharashtra, India. This study evaluates the safety, immunogenicity, and duration of immunity provided by a heterologous vaccine. Additionally, it examines post-vaccination responses in relation to factors such as age, gender, and breed. Methods: This study employed spatiotemporal analysis of lumpy skin disease (LSD) outbreaks from 2020 to 2024 using GeoDa (v1.22), incorporating Moran’s I and Getis-Ord Gi* statistics to identify spatial clustering patterns. A randomized field trial was conducted to evaluate vaccine safety and immunogenicity in 657 cattle across seven districts. Humoral immune responses were assessed using the serum neutralization test (SNT) and indirect enzyme-linked immunosorbent assay (ELISA), while cell-mediated immunity was evaluated via Interferon-gamma (IFN-γ) ELISA. For sero-monitoring, a total of 1925 serum samples from 22 districts were analyzed. Additionally, statistical analyses (n = 1925), including the Kappa Index, ANOVA, and logistic regression, were performed using SPSS v27 to investigate the influence of factors such as age, sex, and breed (significance level: p < 0.05). Results: LSD exhibited significant spatial clustering across Maharashtra. The Goatpox vaccine was 100% safe, with no adverse reactions. Protective antibody titers (≥1:8) were observed in 96.9% of vaccinated cattle by 14–21 days post-vaccination (dpv), peaking at 60 dpv before declining at 150 dpv. The cell-mediated immune response peaked at 28 dpv. Clinical monitoring for one year showed that only 2% of vaccinated cattle developed mild LSD symptoms after nine months, with no mortality. At six months post-vaccination, seroconversion was 69.7%, with breed significantly influencing seropositivity. Conclusions: This study confirms the Goatpox vaccine’s safety and strong immunogenicity in cattle, marking its first large-scale evaluation in the Indian subcontinent. Further research is needed to assess long-term immunity and protection against virulent LSD strains.

An excessive inflammatory response, also known as “cytokine storm,” is a major cause of severe COVID-19. Viral RNA and its structural proteins are key mediators of SARS-CoV-2-induced inflammation. While the immune sensors and host inflammatory responses induced by SARS-CoV-2 RNA and the structural proteins spike (S), envelope (E), and nucleocapsid (N) are well defined, the role of membrane (M) protein in inflammatory/antiviral response and the signaling pathway facilitating M protein-mediated immune response is not well characterized. Here, we show that SARS-CoV-2 M protein induces robust inflammatory cytokine responses in murine and human macrophages and lungs. We also show that the M protein-induced inflammatory response relies on TLR4 signaling and that MyD88 serves as the key adaptor driving inflammation, while TRIF is primarily required for the antiviral IFN response. Detailed evaluation of downstream signaling pathways highlighted the critical roles of mitogen-activated protein kinase (MAPK) molecules JNK and ERK1/2, followed by nuclear factor kappa B (NF-κB) and p38 signaling in the M protein-TLR4-mediated inflammatory response. Finally, we show that abrogation of M protein-induced ERK1/2 and p38 signaling reduced inflammatory cytokine production and rescued type I interferon production in wild-type macrophages, while inhibition of JNK and NF-κB suppressed the M protein-induced inflammatory and antiviral cytokine responses. Collectively, our results demonstrate that SARS-CoV-2 M protein induces pro-inflammatory cytokines and type I interferons via TLR4-MyD88/TRIF activation, with MAPK activation playing a dominant role, and offer specific targeting of MAPK signaling to mitigate SARS-CoV-2-induced excessive inflammation and pathology. IMPORTANCE: Severe COVID-19 is often caused by an excessive inflammatory response, but the role of the SARS-CoV-2 membrane (M) protein in this process has not been well understood. We show that the M protein strongly activates inflammatory and antiviral immune responses through TLR4 signaling and identify the key signaling pathways involved. We also demonstrate that selectively targeting MAPK signaling can reduce harmful inflammation while restoring antiviral interferon responses. These findings improve our understanding of how SARS-CoV-2 causes disease and identify potential therapeutic targets to limit excessive inflammation without compromising antiviral immunity.