African swine fever (ASF) is an acute, highly contagious, and deadly infectious disease. The mortality rate of the most acute and acute ASF infection is almost 100%. The World Organization for Animal Health [Office International des épizooties (OIE)] lists it as a legally reported animal disease and China lists it as class I animal epidemic. Since the first diagnosed ASF case in China on August 3, 2018, it has caused huge economic losses to animal husbandry. ASF is caused by the African swine fever virus (ASFV), which is the only member of Asfarviridae family. ASFV is and the only insect-borne DNA virus belonging to the Nucleocytoplasmic Large DNA Viruses (NCLDV) family with an icosahedral structure and an envelope. Till date, there are still no effective vaccines or antiviral drugs for the prevention or treatment of ASF. The complex viral genome and its sophisticated ability to regulate the host immune response may be the reason for the difficulty in developing an effective vaccine. This review summarizes the recent findings on ASFV structure, the molecular mechanism of ASFV infection and immunosuppression, and ASFV-encoded proteins to provide comprehensive proteomic information for basic research on ASFV. In addition, it also analyzes the results of previous studies and speculations on the molecular mechanism of ASFV infection, which aids the study of the mechanism of clinical pathological phenomena, and provides a possible direction for an intensive study of ASFV infection mechanism. By summarizing the findings on molecular mechanism of ASFV- regulated host cell immune response, this review provides orientations and ideas for fundamental research on ASFV and provides a theoretical basis for the development of protective vaccines against ASFV.

African swine fever—an acute, febrile, hemorrhagic, highly contacting, and highly lethal disease caused by African swine fever virus (ASFV)—jeopardizes the global pig industry. Understanding the mechanism ASFV employs to evade host defense during infection is essential for developing targeted drugs and vaccines against ASFV.

Retinoic acid-inducible gene I (RIG-I) is a pattern recognition receptor and is involved in the innate immune response against RNA viruses infection. Here, we demonstrate that the Ras-GTPase-activating protein SH3-domain-binding protein 1 (G3BP1) serves as a positive regulator of the RIG-I-mediated signaling pathway. G3BP1-deficient cells inhibited RNA virus-triggered induction of downstream antiviral genes. Furthermore, we found that G3BP1 inhibited the replication of Sendai virus and vesicular stomatitis virus, indicating a positive regulation of G3BP1 to cellular antiviral responses. Mechanistically, G3BP1 formed a complex with RNF125 and RIG-I, leading to decreased RNF125 via its auto-ubiquitination; thus, promoting expression of RIG-I. Overall, the results suggest a novel mechanism for G3BP1 in the positive regulation of antiviral signaling mediated by RIG-I.

ASFV is a large DNA virus that is highly pathogenic in domestic pigs. How this virus is sensed by the innate immune system as well as why it is so virulent remains enigmatic. In this study, we show that the ASFV genome contains AT-rich regions that are recognized by the DNA-directed RNA polymerase III (Pol-III), leading to viral RNA sensor RIG-I-mediated innate immune responses. We further show that ASFV protein I267L inhibits RNA Pol-III-RIG-I-mediated innate antiviral responses. I267L interacts with the E3 ubiquitin ligase Riplet, disrupts Riplet-RIG-I interaction and impairs Riplet-mediated K63-polyubiquitination and activation of RIG-I. I267L-deficient ASFV induces higher levels of interferon-β, and displays compromised replication both in primary macrophages and pigs compared with wild-type ASFV. Furthermore, I267L-deficiency attenuates the virulence and pathogenesis of ASFV in pigs. These findings suggest that ASFV I267L is an important virulence factor by impairing innate immune responses mediated by the RNA Pol-III-RIG-I axis.

Ras-GTPase-activating protein (SH3 domain)-binding protein (G3BP) is an RNA binding protein. G3BP is a key component of stress granules (SGs) and can interact with many host proteins to regulate the expression of SGs. As an antiviral factor, G3BP can interact with viral proteins to regulate the assembly of SGs and thus exert antiviral effects. However, many viruses can also use G3BP as a proximal factor and recruit translation initiation factors to promote viral proliferation. G3BP regulates mRNA translation and attenuation to regulate gene expression; therefore, it is closely related to diseases, such as cancer, embryonic death, arteriosclerosis, and neurodevelopmental disorders. This review discusses the important discoveries and developments related G3BP in the biological field over the past 20 years, which includes the formation of SGs, interaction with viruses, stability of RNA, and disease progression.

Foot-and-mouth disease (FMD) is a highly contagious disease, which affects cloven-hoofed animals such as pigs, cattle and sheep. The disease is caused by foot-and-mouth disease virus (FMDV) which has a non-enveloped virion of icosahedral symmetry encapsulating a posi-tive-sense, single-stranded RNA genome of ~8.4 kb. During FMDV in-fection, it has obvious immunosuppressive effects to the host. In recent years, the study on the immunosuppressive mechanism of FMDV has become a hot topic. In addition, studies have shown that many FMDV proteins are involved in the regulation of host innate immunity and re-vealed the mechanisms by which FMDV proteins mediated host innate immunity. In this review, the advance in mechanisms of interaction be-tween FMDV proteins and host’s innate immunity are summarized to provide a reference for comprehensive understanding of FMDV patho-genesis and theoretical basis for FMD prevention and control.