A QP509L/QP383R-Deleted African Swine Fever Virus Is Highly Attenuated in Swine but Does Not Confer Protection against Parental Virus Challenge

African swine fever (ASF), a devastating infectious disease in swine, severely threatens the global pig farming industry. Disease control has been hampered by the unavailability of vaccines. Here, we report that deletion of the QP509L and QP383R genes (ASFV-Delta QP509L/QP383R) from the highly virulent ASF virus (ASFV) CN/GS/2018 strain results in complete viral attenuation in swine. Animals inoculated with ASFV-Delta QP509L/QP383R at a 10(4) 50% hemadsorbing dose (HAD(50)) remained clinically normal during the 17-day observational period. All ASFV-Delta QP509L/QP383R-infected animals had low viremia titers and developed a low-level p30-specific antibody response. However, ASFV-Delta QP509L/QP383R did not induce protection against challenge with the virulent parental ASFV CN/GS/2018 isolate. RNA-sequencing analysis revealed that innate immune-related genes (Ifnb, Traf2, Cxcl10, Isg15, Rantes, and Mx1) were significantly lower in ASFV-Delta QP509L/QP383R-infected than in ASFV-infected porcine alveolar macrophages. In addition, ASFV-Delta QP509L/QP383R-infected pigs had low levels of interferon-beta (IFN-beta) based on enzyme-linked immunosorbent assay (ELISA). These data suggest that deletion of ASFV QP509L/383R reduces virulence but does not induce protection against lethal ASFV challenge. IMPORTANCE African swine fever (ASF) is endemic to several parts of the word, with outbreaks of the disease devastating the swine farming industry; currently, no commercially available vaccine exists. Here, we report that deletion of the previously uncharacterized QP509L and QP383R viral genes completely attenuates virulence in the ASF virus (ASFV) CN/GS/2018 isolate. However, ASFV-Delta QP509L/QP383R-infected animals were not protected from developing an ASF infection after challenge with the virulent parental virus. ASFV-Delta QP509L/QP383R induced lower levels of innate immune-related genes and IFN-beta than the parental virus. Our results increase our knowledge of developing an effective and live ASF attenuated vaccine.

Automated summary

Deletion of the QP509L and QP383R genes from the highly virulent ASF virus completely attenuates the virus in pigs. However, the deleted virus does not provide protection against infection by the virulent parental virus. Additionally, the deleted virus induces lower levels of immune-related genes and interferon-beta.