Inflammatory factors and type I interferons (IFNs) are key components of host antiviral innate immune responses, which can be released from the pathogen-infected macrophages. African swine fever virus (ASFV) has developed various strategies to evade host antiviral innate immune responses, including alteration of inflammatory responses and IFNs production. However, the molecular mechanism underlying inhibition of inflammatory responses and IFNs production by ASFV-encoded proteins has not been fully understood. Here we report that ASFV infection only induced low levels of IL-1β and type I IFNs in porcine alveolar macrophages (PAMs), even in the presence of strong inducers such as LPS and poly(dA:dT). Through further exploration, we found that several members of the multigene family 360 (MGF360) and MGF505 strongly inhibited IL-1β maturation and IFN-β promoter activation. Among them, pMGF505-7R had the strongest inhibitory effect. To verify the function of pMGF505-7R in vivo, a recombinant ASFV with deletion of the MGF505-7R gene (ASFV-Δ7R) was constructed and assessed. As we expected, ASFV-Δ7R infection induced higher levels of IL-1β and IFN-β compared with its parental ASFV HLJ/18 strain. ASFV infection-induced IL-1β production was then found to be dependent on TLRs/NF-κB signaling pathway and NLRP3 inflammasome. Furthermore, we demonstrated that pMGF505-7R interacted with IKKα in the IKK complex to inhibit NF-κB activation and bound to NLRP3 to inhibit inflammasome formation, leading to decreased IL-1β production. Moreover, we found that pMGF505-7R interacted with and inhibited the nuclear translocation of IRF3 to block type I IFN production. Importantly, the virulence of ASFV-Δ7R is reduced in piglets compared with its parental ASFV HLJ/18 strain, which may due to induction of higher IL-1β and type I IFN production in vivo. Our findings provide a new clue to understand the functions of ASFV-encoded pMGF505-7R and its role in viral infection-induced pathogenesis, which might help design antiviral agents or live attenuated vaccines to control ASF.
An emerging infectious disease, severe fever with thrombocytopenia syndrome (SFTS), was identified to be associated with a novel SFTS virus (SFTSV). Transmission of the disease among humans has been described, but clinical impact factors and transmission mechanisms still need further study. An outbreak of person-to-person transmission of SFTS in a cluster of nine patients that occurred in an SFTS endemic area, Penglai County, Shandong province, China, was investigated. We found that the onset date of all eight secondary SFTS patients ranged from 7 to 13 days after exposure to the corpse of the index patient, and clinical incubation time was mostly focused on 9-10 days (n = 6). The two dead patients, including the index patient and one secondary infected patient, presented unusually high levels of viral load (6 × 10(8-9) copies/mL), low levels of platelets count (<55 × 10(9)/L), and significant increase of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and creatine kinase values in the second week, and died on day 10 or 11 after disease onset. Genetic sequencing revealed 100% homology among virus strains isolated from the index patient and five secondary patients. Risk factors assessment of the person-to-person transmission revealed that the major exposure factor was blood contact without personal protection equipment. Information from this study provided solid references of SFTS incubation time, clinical and laboratory parameters related to SFTS severity and outcome, and biosafety issues for preventing person-to-person transmission or nosocomial infection of SFTSV.
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