Xiangyu Guan,Tao Wang,Yuxuan Gao,Huanjie Zhai,Fengwei Jiang,Qinghe Hou,Xiaoke Yang,Hongxia Wu,Lian-Feng Li,Yuzi Luo,Su Li,Yuan Sun,Hua-Ji Qiu,Yongfeng Li
J Virol.2024 Dec 23:e0144524.doi: 10.1128/jvi.01445-24. Online ahead of print.
Abstract
African swine fever (ASF) is a highly contagious and often lethal disease caused by African swine fever virus (ASFV) in pigs. Protein palmitoylation is a prevalent posttranslational lipid modification that can modulate viral replication. In this study, we investigated the palmitoylation of ASFV proteins. The results revealed that the CP123L protein (pCP123L) of ASFV was palmitoylated at the cysteine residue at position 18 (C18). To further elucidate the functional significance of this posttranslational modification, abolishing palmitoylation through a cysteine-to-serine mutation at C18 (C18S) of pCP123L (pCP123L/C18S) or treatment with 2-bromopalmitate (2-BP), a palmitoylation inhibitor, led to altered cytomembrane localization and migration rate of pCP123L. Furthermore, depalmitoylation achieved through 2-BP treatment significantly suppressed ASFV replication and exerted a profound impact on virus budding. Remarkably, blocking pCP123L palmitoylation via the C18S mutation resulted in decreased replication of ASFV. Our study represents the first evidence for the presence of palmitoylation in ASFV proteins and underscores its crucial role in viral replication.
Importance: African swine fever (ASF) poses a significant threat to the global pig industry. The causative agent of ASF is African swine fever virus (ASFV), which encodes more than 165 proteins. Protein palmitoylation, a common posttranslational lipid modification, can modulate viral infection. To date, the ASFV proteins that undergo palmitoylation and their impacts on viral replication remain elusive. In this study, the CP123L protein (pCP123L) of ASFV was identified as a palmitoylated protein, and the cysteine residue at position 18 of pCP123L is responsible for its palmitoylation. Notably, our findings demonstrate that palmitoylation plays significant roles in ASFV protein functions and facilitates viral replication.
Keywords: African swine fever virus; CP123L protein; budding; palmitoylation; replication.