title: Targeted disruption of CK1α in Toxoplasma gondii increases acute virulence in mice.
abstract: Toxoplasma gondii, the causative agent of toxoplasmosis, encodes two casein kinase 1 (CK1) isoforms, CK1α and CK1β, with only CK1α having enzyme activity. Here we investigated the biological role of CK1α by construction of a CK1α deletion mutant (Δck1α) based on the type I parasite, and complement the mutant with restored expression of CK1α. Deletion of CK1α resulted in markedly defective parasite replication in vitro. Infected mice with Δck1α parasite caused suppression of IL-12 production, severe liver damage, higher tissue burdens, and short survival time relative to the CK1α-positive parental strain. Western blot analysis revealed that deletion of CK1α led to increased activation of the signal transducer and activator of transcription (STAT)-3 in infected mice and bone marrow-derived microphages. The transcriptome analysis showed that deletion of CK1α may increase expression of rhoptry proteins (ROPs). Western blot showed enhanced expression of ROP16 in the Δck1α parasite as compared with the wild-type and complemented parasites. These findings demonstrated that deletion of CK1α may increase acute virulence of T. gondii in mice by increased expression of ROPs, activation of STAT3, and suppression of IL-12 production, which have important implications for elucidating regulation mechanism of virulence factors for T. gondii.
authors: Military Veterinary Institute, Academy of Military Medical Sciences, Key Laboratory of Jilin Province for Zoonosis Prevention and Control, 666 Liuying West Road, Changchun 130122, Jilin Province, China.
authors: Zedong
authors: Z
authors: Wang
authors: Military Veterinary Institute, Academy of Military Medical Sciences, Key Laboratory of Jilin Province for Zoonosis Prevention and Control, 666 Liuying West Road, Changchun 130122, Jilin Province, China.
authors: Shuchao
authors: S
authors: Wang
authors: Military Veterinary Institute, Academy of Military Medical Sciences, Key Laboratory of Jilin Province for Zoonosis Prevention and Control, 666 Liuying West Road, Changchun 130122, Jilin Province, China.
authors: Wei
authors: W
authors: Wang
authors: Military Veterinary Institute, Academy of Military Medical Sciences, Key Laboratory of Jilin Province for Zoonosis Prevention and Control, 666 Liuying West Road, Changchun 130122, Jilin Province, China.
authors: Yi
authors: Y
authors: Gu
authors: College of Life Science, Jilin Agricultural University, 2888 Xincheng Street, Changchun 130118, Jilin Province, China.
authors: Huanhuan
authors: H
authors: Liu
authors: Military Veterinary Institute, Academy of Military Medical Sciences, Key Laboratory of Jilin Province for Zoonosis Prevention and Control, 666 Liuying West Road, Changchun 130122, Jilin Province, China; College of Life Science, Jilin Agricultural University, 2888 Xincheng Street, Changchun 130118, Jilin Province, China.
authors: Feng
authors: F
authors: Wei
authors: Military Veterinary Institute, Academy of Military Medical Sciences, Key Laboratory of Jilin Province for Zoonosis Prevention and Control, 666 Liuying West Road, Changchun 130122, Jilin Province, China. Electronic address: liuquan1973@hotmail.com.
authors: Quan
authors: Q
authors: Liu
mesh_terms: D000818:Animals; D047389:Casein Kinase I / Q000235:genetics*; D002460:Cell Line; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism; D008099:Liver / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000235:genetics; D016019:Survival Analysis; D014122:Toxoplasma / Q000201:enzymology / Q000235:genetics* / Q000472:pathogenicity*; D014123:Toxoplasmosis / Q000401:mortality / Q000469:parasitology* / Q000473:pathology; D059467:Transcriptome; D014709:Vero Cells; D014774:Virulence / Q000235:genetics*
chemical_list: D015800:Protozoan Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D018664:Interleukin-12; D047389:Casein Kinase I
keywords: CK1α; IL-12; Mice; ROP16; Toxoplasma gondii; Virulence