Lumpy skin disease virus enters into host cells via dynamin-mediated endocytosis and macropinocytosis.

Lumpy skin disease virus (LSDV), a ruminant poxvirus of the Capripoxvirus genus, is the etiologic agent of an economically important cattle disease categorized as a notifiable disease by the World Organization for Animal Health. However, the endocytic pathway and their regulatory molecules have not been characterized for LSDV. In the present study, specific pharmacological inhibitors were used to analyze the mechanism of LSDV entry into Mardin-Darby Bovine Kidney cell (MDBK) and bovine mammary epithelial cell (BMEC). The results showed that LSDV entered MDBK and BMEC cells depends on low-pH conditions and dynamin. However, the inhibitor of caveolae- and clathrin-mediated endocytosis cann't inhibit LSDV entry into MDBK and BMEC cells. Furthermore, treatment with specific inhibitors demonstrated that LSDV entry into MDBK and BMEC cells via macropinocytosis depended on the Na1/H1 exchanger (NHE) but not phosphatidylinositol 3-kinase (PI3K). In addition, results demonstrated that these inhibitors inhibited LSDV entry but did not have effect on LSDV binding. Taken together, our study demonstrated that LSDV enters MDBK and BMEC cells through macropinocytosis pathway in a low-PH- and dynamin-dependent manner while independent on PI3K. Results presented in this study potentially provides insight into the entry mechanisms of LSDV, and it may facilitate the development of therapeutic interventions.

Foot-and-Mouth Disease Virus Capsid Protein VP1 Antagonizes Type I Interferon Signaling via Degradation of Histone Deacetylase 5.

Foot-and-mouth disease (FMD) is a highly contagious and economically important disease of cloven-hoofed animals that hampers trade and production. To ensure effective infection, the foot-and-mouth disease virus (FMDV) evades host antiviral pathways in different ways. Although the effect of histone deacetylase 5 (HDAC5) on the innate immune response has previously been documented, the precise molecular mechanism underlying HDAC5-mediated FMDV infection is not yet clearly understood. In this study, we found that silencing or knockout of HDAC5 promoted FMDV replication, whereas HDAC5 overexpression significantly inhibited FMDV propagation. IFN-ß and IFN-stimulated response element (ISRE) activity was strongly activated through the overexpression of HDAC5. The silencing and knockout of HDAC5 led to an increase in viral replication, which was evident by decreased IFN-ß, ISG15, and ISG56 production, as well as a noticeable reduction in IRF3 phosphorylation. Moreover, the results showed that the FMDV capsid protein VP1 targets HDAC5 and facilitates its degradation via the proteasomal pathway. In conclusion, this study highlights that HDAC5 acts as a positive modulator of IFN-ß production during viral infection, while FMDV capsid protein VP1 antagonizes the HDAC5-mediated antiviral immune response by degrading HDAC5 to facilitate viral replication.

Adverse events of Oxford/AstraZeneca's COVID-19 vaccine among health care workers of Ayder Comprehensive Specialized Hospital, Tigray, Ethiopia.

Background: : The safety of COVID vaccines should be continuously followed. This study reports adverse events of the Oxford/AstraZeneca COVID-19 vaccine. Methods: : A prospective single-cohort study design was conducted to assess adverse events following immunization and associated factors of the first dose of Oxford/AstraZeneca's COVID-19 vaccine in Ayder Comprehensive specialized hospital. A structured questionnaire was administered consecutively to 423 participants. Follow-up data were collected 72 hours after vaccination via phone. Bivariate and multivariate logistic regression models were used to find associations between adverse events and independent variables. Statistical significance was declared at P<0.05. Results: : Out of 423 health care workers approached, 395 responded. At least one adverse event (95% CI: 63.58, 72.77) was reported by 270 participants. Local and systemic symptoms occurred in 46.8% (95% CI: 41.94, 51.79) and 58.48% (95% CI: 53.53, 63.26)], respectively. Muscle ache, fatigue, headache and fever were the most common local symptoms. No reports of hospitalization, disability or death. Age (adjusted odds ratio [AOR]=0.97, P=0.048), female sex (AOR=1.84, P=0.028), and comorbidity (AOR=2.28, P=0.040) were independent predictors of adverse events. Conclusion and recommendation: : Adverse events following immunization are commonly reported after the first dose of the Oxford/AstraZeneca COVID-19 vaccine; age, female sex and comorbidity are independent predictors.