Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: October 29, 2003
Publication Date: March 20, 2004
Citation: Burrage, T.G., Lu, Z., Neilan, J.G., Rock, D.L., Zsak, L. 2004. African swine fever virus multigene family 360 genes affect virus replication and generalization of infection in ornithodoros porcinus ticks. Journal of Virology. 78(5):2445-2453. Interpretive Summary: African swine fever virus (ASFV) cycles between two hosts, the warthog and the soft tick (Omithodoros porcinus) in sub-Saharan Africa. Infection of tick host results in a gradual amplification, followed by a generalization and a life-long persistence of the virus. Viral factors responsible for the successful infection of ticks with different ASFV isolates are unknown. Here, for the first time we identified ASF viral genes required for efficient replication and generalization of infection in the tick host. Our results indicate that ASFV multigene family 360 genes are significant host range determinants and are essential for viral replication in the tick host. Identification of critical viral virulence and host range genes of ASFV in different hosts will provide the information necessary for engineering attenuated viral strains as possible vaccine candidates, and it will likely suggest novel approaches for disease control.
Technical Abstract: Recently, we reported that African swine fever virus (ASFV) multigene family (MGF) 360 and 530 genes are significant swine macrophage host range determinants functioning by promoting infected cell survival. To examine the function of these genes in ASFV's arthropod host, Ornithodorosporcinusporcinus, an MGF360/530 gene deletion mutant (Delta 35) was constructed from an ASFV isolate of tick origin, Pr4. Delta 35 exhibited a significant growth defect in ticks. Deletion of six MGF360 and two MGF530 genes from Pr4 markedly reduced viral replication in infected ticks by 100- to 1,000-fold. To define the minimal set of MGF360/530 genes required for tick host range, additional gene deletion mutants lacking individual or multiple MGF genes were constructed. Pr4 deletion mutant 3-C2, which lacked three MGF360 genes (3HL, 3IL, 3LL) exhibited reduced viral growth in ticks. Titers of 3-C2 virus in ticks were significantly reduced by 100- to 1,000-fold over control values at times post infection. In contrast to parental virus where high levels of virus replication was observed in tissues of infected adults, 3-C2 replication was not detected in midgut, hemolymph, salivary gland, coxal gland, and reproductive organs at 15 weeks post 'infection. These data indicate that ASFV MGF360 genes are significant tick host range determinants and that they are required for efficient virus replication and generalization of infection. hnpaired virus replication of 3-C2 in tick midgut likely accounts for the absence of generalized infection that is necessary for natural transmission of virus from tick to pig.