State Key Laboratory for Animal Disease Control and Prevention, National High Containment Facilities for Animal Diseases Control and Prevention, Harbin Veterinary Research Institute, CAAS, Harbin, People's Republic of China.
Institute of Western Agriculture, CAAS, Changji, People's Republic of China.
Emerg Microbes Infect. 2024 Dec;13(1):2377599. doi: 10.1080/22221751.2024.2377599. Epub 2024 Jul 18.
African swine fever virus (ASFV) is the causative agent of African swine fever (ASF), a highly contagious disease that can kill up to 100% of domestic pigs and wild boars. It has been shown that the pigs inoculated with some ASF vaccine candidates display more severe clinical signs and die earlier than do pigs not immunized. We hypothesize that antibody-dependent enhancement (ADE) of ASFV infection may be caused by the presence of some unidentified antibodies. In this study, we found that the ASFV-encoded structural protein A137R (pA137R) can be recognized by the anti-ASFV positive sera, indicating that the anti-pA137R antibodies are induced in the ASFV-infected pigs. Interestingly, our results demonstrated that the anti-pA137R antibodies produced in rabbits or pigs enhanced viral replication of different ASFV strains in primary porcine alveolar macrophages (PAMs), the target cells of ASFV. Mechanistic investigations revealed that anti-pA137R antibodies were able to promote the attachment of ASFV to PAMs and two types of Fc gamma receptors (FcRs), FcRII and FcRIII, mediated the ADE of ASFV infection. Taken together, anti-pA137R antibodies are able to drive ASFV ADE in PAMs. These findings shed new light on the roles of anti-ASFV antibodies and have implications for the pathophysiology of the disease and the development of ASF vaccines.
非洲猪瘟病毒（ASFV）是非洲猪瘟（ASF）的病原体，这是一种高度传染性疾病，可导致家猪和野猪的死亡率高达 100%。已经表明，接种某些 ASF 疫苗候选物的猪比未免疫的猪表现出更严重的临床症状并更早死亡。我们假设 ASFV 感染的抗体依赖性增强（ADE）可能是由一些未识别的抗体引起的。在这项研究中，我们发现 ASFV 编码的结构蛋白 A137R（pA137R）可被抗 ASFV 阳性血清识别，表明在 ASFV 感染的猪中诱导了抗 pA137R 抗体。有趣的是，我们的结果表明，在兔或猪中产生的抗 pA137R 抗体增强了不同 ASFV 株在原代猪肺泡巨噬细胞（PAMs）中的病毒复制，PAMs 是 ASFV 的靶细胞。机制研究表明，抗 pA137R 抗体能够促进 ASFV 与 PAMs 的附着，并且两种类型的 Fcγ受体（FcR），FcRII 和 FcRIII，介导了 ASFV 感染的 ADE。总之，抗 pA137R 抗体能够在 PAMs 中驱动 ASFV 的 ADE。这些发现为抗 ASFV 抗体的作用提供了新的认识，并对疾病的病理生理学和 ASF 疫苗的开发具有重要意义。
