Infection of human macrophage-like cells by African swine fever virus

Abstract

Abstract African swine fever (ASF) virus (ASFV) and ASF-like viral sequences were identified in human samples and sewage as well as in different water environments. Pigs regularly experience infections with ASF virus. The considerable stability of the virus in the environment suggests that there is ongoing and long-term contact between humans and the ASF virus. However, humans exhibit resistance to the ASF virus, and the decisive factor in the development of infection in the body is most likely the reaction of target macrophages to the virus. Therefore, the aim of this study was to characterize the response of human macrophages to the virus and explore the distinct features of the viral replication cycle within human macrophages. Our findings have shown that the virus effectively initiated the replication process by entering human macrophages. Subsequently, the virus shed its capsid, initiated the transcription of numerous viral genes, and at least some of these genes executed their functions. In THP-1-derived macrophages (Mφ0), ASFV implemented a number of functions to suppress cell activity, but the timing of their implementation was slower compared to virus-sensitive porcine alveolar macrophages (PAMs). Besides, the virus was unable to complete the full replication cycle in human Mφ0, as indicated by the absence of viral factories and a decrease in infectious titers of the virus with each subsequent passage. Overall, the infection of Mφ0 with ASFV caused significant alterations in their phenotype and functions such as increased TLR2, TLR3, CD80, CD36, CD163, CXCR2, and surface LAMP-1 expression. Increased production of TNF, IL-10, and decreased production of IFN-α were also observed. Taken together, the virus enters human THP-1-derived macrophages, starts transcription, and causes a response from target cells, but is unable to complete the replicative cycle.