Molecular Immunology 73 (2016) 122–129 Contents lists available at ScienceDirect Molecular Immunology j ourna l ho me pa g e : www.elsevier.com/locate/molimm Important roles played by TGF- member of Bmdpp and Bmdaw in BmNPV infection Xiaolong Hu a,b,1 , Yue Jiang a,1 , Yongchang Gong a , Min Zhu a , Liyuan Zhu a , Fei Chen a , Zi Liang a , Sulan Kuang a , Mian Sahib Zar a , Dhiraj Kumar a , Guangli Cao a,b , Renyu Xue a,b , Chengliang Gong a,b,∗ a School of Biology & Basic Medical Science, Soochow University, Suzhou 215123, China b National Engineering Laboratory for Modern Silk, Soochow University, Suzhou 215123, China a r t i c l e i n f o Article history: Received 11 February 2016 Received in revised form 6 April 2016 Accepted 6 April 2016 Keywords: Bombyx mori TGF-&beta decapentaplegic dawdle BmNPV a b s t r a c t Transforming growth factor (TGF)- superfamily members inhibit Bombyx mori nucleohedrovirus (BmNPV) multiplication in silkworm are not determined. In this study, we first found that BmNPV RNA transcription and protein expression level were regulated by TGF- members, Decapentaplegic (Bmdpp) and Dawdle (Bmdaw) in the domesticated silkworm, B. mori and silkworm ovary-derived cells. Further- more, subcellular localization showed that Bmdpp and Bmdaw were mainly presented in cytomembrane of the cultured BmN cells. Tissues expression pattern analysis found that the highest expression levels of Bmdpp and Bmdaw genes were in the hemocyte of fifth instar larvae. During the immune response, the expression level of Bmdpp gene was elevated and Bmdaw gene was declined in BmNPV infected BmN cells and silkworm. The multiplication of BmNPV was inhibited by overexpression of Bmdpp and Bmdaw genes in BmN cells. RNA interference experiments found that the multiplication of BmNPV was raised with specific siRNAs of Bmdpp and Bmdaw genes in BmN cells. The antiviral immune pathways were not significantly regulated by the TGF- superfamily members. Taken together, these findings provided a clue to understand the function of Bmdpp and Bmdaw gene in response to the BmNPV infection in silkworm. © 2016 Published by Elsevier Ltd. 1. Introduction The transforming growth factor  (TGF-) superfamily mem- bers consist of over 30 members such as growth and differentiation factors (GDFs), Activins, Nodal and bone morphogenetic proteins (BMPs). They have vital role in the proliferation, self-renewal, development, growth, immune responses, lifespan of stem cells and homeostasis of metazoans (Feng and Derynck, 2005). TGF- signaling pathways have been extensively studied which assumed that TGF- ligands and downstreaming pathways remain similar with reference to the evolutionary point of view. They con- trol and regulate diverse cellular functions in mammals as an important check point. During the embryonic development the actions of TGF- is modulated timely, leading to a triggering of a variety in cellular responses (Wu and Hill, 2009). Homologous TGF- family members were determined from the humans and all ∗ Corresponding author at: School of Biology & Basic Medical Science, Soochow University, Suzhou 215123, China. E-mail address: gongcl@suda.edu.cn (C. Gong). 1 These authors contributed equally to this work. animal model organisms with phylogenetic studies and interspe- cific experiments (Johnson and Newfeld, 2002). TGF- strongly induces integrin expression, extracellular matrix synthesis, and modulation of immune responses (Letterio and Roberts, 1998). TGF- superfamily members, decapentaplegic (dpp) and dawdle (daw) constitue major functions in response to wounding and infec- tion in adult Drosophila (Clark et al., 2011). In addition these TGF- members perform a significant role during several distinct stages of Drosophila development (Hadar et al., 2012; Hevia and de Celis, 2013; Li et al., 2013). Two mammalian homologs of the dpp gene were found during the purification of factors which induce the establishment of ectopic bone and cartilage when introduced under the skin or into muscles (Wozney et al., 1988). The mammalian fac- tors, BMP2 and BMP4 are 90% identical to each other in the mature signaling portion of the molecule and 75% identical to dpp. Human BMP4 sequences can rescue the dorsoventral axis defects caused by dpp mutations in Drosophila (Padgett et al., 1993). Recent studies have revealed the significant roles of Activin ligands in controlling the development and function of neuron. Like the BMPs, Activin belong to the evolutionarily conserved TGF- superfamily. Daw- dle (Daw) is an example of Activin, which has been genetically http://dx.doi.org/10.1016/j.molimm.2016.04.004 0161-5890/© 2016 Published by Elsevier Ltd.