African Swine Fever Virus Exhibits Distinct Replication Defects in Different Cell Types

Abstract

African swine fever virus (ASFV) causes one of the most devastating diseases affecting pigs and wild suids, a worldwide epizootic situation exacerbated in recent years due to the lack of vaccine or effective treatment. ASFV has a restricted cell tropism, and is prone to replicate in porcine monocytes and alveolar macrophages with high efficiency. Here, the replication capabilities of ASFV were examined in swine pulmonary alveolar macrophages (PAMs) and compared with 3D4/21, PK−15, MA−104 and Marc−145 cell lines using PCR, qPCR and Western blot with monoclonal antibodies against the viral p30 and p72 proteins. The results showed that ASFV has a variety of infection characteristics in PAMs and showed four cell lines with distinct defects during virus early transcription−translation, genome replication and late protein synthesis. Furthermore, an antiviral role of the stress granule pathway was revealed against ASFV, and ASFV infection inhibited stress granule formation in PAMs but not 3D4/21. These results will help to deepen our knowledge on ASFV infection and to develop ASFV susceptible cell lines.

CA-CAS-01-A: A Permissive Cell Line for Isolation and Live Attenuated Vaccine Development Against African Swine Fever Virus

“…Suitable in vitro systems for the detection, isolation, and manipulation of field isolates of pathogenic ASFV are only available for porcine primary macrophages and monocytes derived from peripheral blood or other tissues (Meloni et al, 2022 ). The quality of primary cell preparations may vary from batch to batch due to differences in the health of donor animals and preparation techniques, and the generation of primary macrophages is time-consuming and expensive and can result in contamination leading to cell waste (Gao et al, 2022 ). Moreover, using primary cells to produce large-scale vaccines is ethically challenging and, therefore, not feasible.…”

“…Moreover, using primary cells to produce large-scale vaccines is ethically challenging and, therefore, not feasible. Consequently, the development of safe and effective ASFV vaccines and diagnosis has been hampered by the lack of continuous cell lines suitable for ASFV isolation and propagation (Gao et al, 2022 ; Masujin et al, 2021 ). In light of these obstacles, the development of sustainable cell lines susceptible to ASFV infection is urgently needed.…”

A Cell-Adapted Live-Attenuated Vaccine Candidate Protects Pigs against the Homologous Strain VNUA-ASFV-05L1, a Representative Strain of the Contemporary Pandemic African Swine Fever Virus

“…It has been reported that 3D4/21 can support the growth of cell-adapted ASFV-Lisbon 61 and field isolate Lillie SI/85 [ 31 , 32 ], but it was unable to maintain replication of the genotype II ASFV-HLJ/18 strain [ 33 ]. However, a more recent study showed that the ASFV genotype II strain CN/GS/2018 can attach and enter 3D4/21 cells, resulting in genome replication rate of up to 10 6 copies/mL [ 34 ]. Our result is consistent with this study.…”

A Cell-Adapted Live-Attenuated Vaccine Protects Pigs against the Contemporary Pandemic African Swine Fever Virus

“…It has been reported that 3D4/21 can support the growth of celladapted ASFV-Lisbon 61 and field isolate Lillie SI/85 [30,31], but was unable to maintain replication of the genotype II ASFV-HLJ/18 strain [32]. However, a more recent study showed that the ASFV genotype II strain CN/GS/2018 can attach and enter into 3D4/21 cells and proceed to genome replication up to 10 6 copies/ml [33]. Our result is consistent with this study.…”