Xiaoke Yang,Encheng Sun,Huanjie Zhai,Tao Wang,Shida Wang,Yuxuan Gao,Qinghe Hou,Xiangyu Guan,Shuwen Li,Lian-Feng Li,Hongxia Wu,Yuzi Luo,Su Li,Yuan Sun,Dongming Zhao,Yongfeng Li,Hua-Ji Qiu

Emerg Microbes Infect.2024 Jul 8:2377599.doi: 10.1080/22221751.2024.2377599. Online ahead of print.

Abstract

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 (Fc γ Rs), Fc γ RII and Fc γ RIII, 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.

Keywords: A137R protein; African swine fever virus; Antibody-dependent enhancement; Fc gamma receptors; Viral replication.