title: Tongue sole (Cynoglossus semilaevis) prothymosin alpha: Cytokine-like activities associated with the intact protein and the C-terminal region that lead to antiviral immunity via Myd88-dependent and -independent pathways respectively.
abstract: Prothymosin alpha (ProTα) is a small protein that in mammals is known to participate in diverse biological processes including immunomodulation. In teleost, the immunological function of ProTα is unknown. In the current study, we investigated the expression and function of the ProTα (named CsProTα) from the teleost fish tongue sole (Cynoglossus semilaevis). We found that CsProTα expression was abundant in immune relevant tissues and upregulated by megalocytivirus infection. Immunoblot detected secretion of CsProTα by peripheral blood leukocytes. Recombinant CsProTα (rCsProTα) as well as the C-terminal 11-residue (Ct11) were able to bind head kidney monocytes (HKM) and induce immune gene expression; however, the induction patterns caused by rCsProTα and Ct11 differed considerably. When introduced in vivo, rCsProTα and Ct11 significantly reduced megalocytivirus infection in fish tissues, whereas rCsProTα antibody significantly promoted viral replication. Blocking of Myd88 activity abolished the virus-inhibitory effect of rCsProTα but not Ct11. Taken together, these results demonstrate for the first time that both the intact protein and the C-terminal segment of a teleost ProTα can act like cytokines and induce antiviral immunity via, however, distinct signaling pathways that differ in the requirement of Myd88.
authors.affiliation: Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China.
authors.forename: Bao-cun
authors.initials: BC
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China. Electronic address: lsun@qdio.ac.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Sun
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016207:Cytokines / Q000276:immunology; D005393:Fish Diseases / Q000276:immunology* / Q000821:virology; D005412:Flatfishes / Q000276:immunology* / Q000821:virology; D007497:Iridoviridae / Q000276:immunology*; D008969:Molecular Sequence Data; D053594:Myeloid Differentiation Factor 88 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011498:Protein Precursors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000276:immunology; D013947:Thymosin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D053594:Myeloid Differentiation Factor 88; D011498:Protein Precursors; D011994:Recombinant Proteins; C040782:prothymosin alpha; D013947:Thymosin
keywords: Antiviral; Cynoglossus semilaevis; Immunoregulation; Prothymosin