Contents lists available at ScienceDirect Virus Research journal homepage: www.elsevier.com/locate/virusres Structural and functional modeling of viral protein 5 of Infectious Bursal Disease Virus Bhaskar Ganguly ⁎ , Sunil Kumar Rastogi Animal Biotechnology Center, Department of Veterinary Physiology and Biochemistry, College of Veterinary and Animal Sciences, G. B. Pant University of Agriculture and Technology, Pantnagar, Uttarakhand, 263145, India ARTICLE INFO Keywords: Infectious bursal disease virus Viral protein 5 Function In silico Structure ABSTRACT Infectious Bursal Disease (IBD) is an acute, highly contagious and immunosuppressive disease of young chicken. The causative virus (IBDV) is a bi-segmented, double-stranded RNA virus. The virus encodes five major proteins, viral protein (VP) 1–5. VPs 1–3 have been characterized crystallographically. Albeit a rise in the number of studies reporting successful heterologous expression of VP5 in recent times, challenging the notion that rapid death of host cells overexpressing VP5 disallows obtaining sufficiently pure preparations of the protein for crystallographic studies, the structure of VP5 remains unknown and its function controversial. Our study de- scribes the first 3D model of IBD VP5 obtained through an elaborate computational workflow. Based on the results of the study, IBD VP5 can be predicted to be a structural analog of the leucine-rich repeat (LRR) family of proteins. Functional implications arising from structural similarity of VP5 with host Toll-like receptor (Tlr) 3 also satisfy the previously reported opposing roles of the protein in first abolishing and later inducing host-cell apoptosis. 1. Introduction Infectious Bursal Disease (IBD) is one of the economically most important and common diseases of poultry. It is an acute, highly con- tagious and immunosuppressive viral disease of young chicken, char- acterized by the destruction of dividing lymphoid cells in the bursa of Fabricius causing cytolysis leading to immunosuppression, in addition to losses due to impaired growth and death, and excessive condemna- tions of carcasses because of skeletal muscle hemorrhages (Eterradossi and Saif, 2013). IBD is caused by a virus (IBDV) of the genus Avibirnavirus of Birnaviridae family. The family Birnaviridae is represented by non-en- veloped, icosahedral viruses having a double-stranded RNA genome with two segments A and B. Five major viral proteins (VP) have been identified in IBDV and they are generally referred to as VP 1–5. The smaller genome segment B, about 2.8 kb in size, encodes the RNA-de- pendent RNA polymerase, VP1. Genome segment A, about 3.2 kb in size, encodes a bicistronic mRNA containing two largely overlapping open reading frames (ORFs), A1 and A2. The larger ORF, A2, encodes a polyprotein in the form N-pVP2-VP4-VP3-C that is autoproteolytically cleaved by the viral protease, VP4, to form VP2, VP3, and VP4. VP2 and 3 are structural proteins occurring in the viral capsid. ORF A1 encodes a 17 kDa, non-structural VP5, which occurs only in infected cells (Eterradossi and Saif, 2013). Earlier results suggest two factors that may have discouraged obtaining sufficient amounts of the purified protein as required for crystallographic studies: first, VP5 may not always be ex- pressed by the virus in cell culture, and second, heterologous over- expression of the protein causes the death of the host cells. Notwith- standing the first factor, lately, there has been an increase in the number of studies that report expression of VP5 in cell culture (Mendez et al., 2017). Nevertheless, the structure of IBD VP5 remains unknown and its function is controversial. VP5 is non-essential for virus re- plication in vitro (Mundt et al., 1997) or in vivo (Yao et al., 1998) but necessary for viral release from infected cells (Wu et al., 2009). VP5 is known to prevent apoptosis of the infected host cell during early stages (Liu and Vakharia, 2006) by interacting with the p85α subunit of the phosphatidylinositol 3-kinase (PI3K) (Wei et al., 2011) but promote apoptosis in later stages by interacting with voltage-dependent anion channel 2 polypeptide (VDAC2) (Li et al., 2012). In the present communication, we utilize a combination of several computational methods to derive a structural and functional model of IBD VP5. https://doi.org/10.1016/j.virusres.2018.01.017 Received 2 November 2017; Received in revised form 28 January 2018; Accepted 31 January 2018 ⁎ Corresponding author at: Clinical Research Division, Research and Development Department, Ayurvet Limited, Katha, 173205, Himachal Pradesh, India. E-mail address: vetbhaskar@gmail.com (B. Ganguly). Virus Research 247 (2018) 55–60 Available online 07 February 2018 0168-1702/ © 2018 Elsevier B.V. All rights reserved. T