Franzoni Giulia, Graham Simon P, Giudici Silvia Dei, Bonelli Piero, Pilo Giovannantonio, Anfossi Antonio G, Pittau Marco, Nicolussi Paola S, Laddomada Alberto, Oggiano Annalisa
Department of Veterinary Medicine, University of Sassari, Sassari, 07100, Italy; Istituto Zooprofilattico Sperimentale della Sardegna, Sassari, 07100, Italy.
School of Veterinary Medicine, University of Surrey, Guildford, GU2 7AL, United Kingdom; The Pirbright Institute, Ash Road, Pirbright, GU24 0NF, United Kingdom.
Vet Microbiol. 2017 Jan;198:88-98. doi: 10.1016/j.vetmic.2016.12.010. Epub 2016 Dec 10.
African swine fever (ASF) is a devastating disease for which there is no vaccine available. The ASF virus (ASFV) primarily infects cells of the myeloid lineage and this tropism is thought to be crucial for disease pathogenesis. A detailed in vitro characterization of the interactions of a virulent Sardinian isolate (22653/14) and a tissue culture adapted avirulent strain (BA71V) of ASFV with porcine monocytes, un-activated (moMΦ), classically (moM1) and alternatively (moM2) activated monocyte-derived macrophages was conducted in an attempt to better understand this relationship. Using a multiplicity-of-infection (MOI) of 1, both viruses were able to infect monocytes and macrophage subsets, but BA71V presented a reduced ability to infect moM1 compared to 22653/14, with higher expression of early compared to late proteins. Using an MOI of 0.01, only 22653/14 was able to replicate in all the macrophage subsets, with initially lowest in moM1 and moM2. No differences were observed in the expression of CD163 between ASFV infected and uninfected bystander cells. ASFV down-regulated CD16 expression but did not modulate MHC class II levels in monocytes and macrophage subsets. BA71V-infected but not 22653/14-infected moMΦ and moM2 presented with a reduced expression of MHC class I compared to the mock-infected controls. Higher levels of IL-18, IL1-β and IL-1α were released from moM1 after infection with BA71V compared to 22653/14 or mock-infected control. These results revealed differences between these ASFV strains, suggesting that virulent isolates have evolved mechanisms to counteract activated macrophages responses, promoting their survival, dissemination in the host and so ASF pathogenesis.
非洲猪瘟（ASF）是一种毁灭性疾病，目前尚无可用疫苗。非洲猪瘟病毒（ASFV）主要感染髓系谱系细胞，这种嗜性被认为对疾病发病机制至关重要。为了更好地理解这种关系，对一株强毒撒丁岛分离株（22653/14）和一株适应组织培养的无毒株（BA71V）的ASFV与猪单核细胞、未激活的（moMΦ）、经典激活的（moM1）和替代激活的（moM2）单核细胞衍生巨噬细胞之间的相互作用进行了详细的体外表征。使用感染复数（MOI）为1时，两种病毒都能够感染单核细胞和巨噬细胞亚群，但与22653/14相比，BA71V感染moM1的能力降低，早期蛋白表达高于晚期蛋白。使用MOI为0.01时，只有22653/14能够在所有巨噬细胞亚群中复制，最初在moM1和moM2中最低。在ASFV感染和未感染的旁观者细胞之间，未观察到CD163表达的差异。ASFV下调CD16表达，但未调节单核细胞和巨噬细胞亚群中的MHC II类水平。与模拟感染对照相比，BA71V感染但22653/14未感染的moMΦ和moM2呈现出MHC I类表达降低。与22653/14或模拟感染对照相比，BA71V感染后，moM1释放的IL-18、IL1-β和IL-1α水平更高。这些结果揭示了这些ASFV毒株之间的差异，表明强毒分离株已经进化出对抗激活巨噬细胞反应的机制，促进它们在宿主中的存活、传播以及ASF的发病机制。
