Vol.:(0123456789) 1 3 Archives of Virology https://doi.org/10.1007/s00705-018-3987-3 ORIGINAL ARTICLE Identifcation of a conserved neutralizing epitope in the G‑protein of Chandipura virus Daya V. Pavitrakar 1  · Rekha G. Damle 1  · Anuradha S. Tripathy 1  · Pratip Shil 1 Received: 18 April 2018 / Accepted: 14 June 2018 © Springer-Verlag GmbH Austria, part of Springer Nature 2018 Abstract Chandipura virus (CHPV), associated with an encephalitic illness in humans, has caused multiple outbreaks with high mortality in central and western India in recent years. The present study compares surface glycoprotein (G-protein) from prototype and recent outbreak strains using in silico tools and in vitro experiments. In silico epitope predictions (B-cell and T-helper cell) for the sequences, 3D structure prediction and comparison of the G-proteins of the strains: I653514 (Year 1965), CIN0327 (Year 2003) and 148974 (Year 2014) revealed that the CHPV G-protein is stable and antigenic determinants are conserved. A monoclonal antibody developed against strain CIN0327 (named NAbC) was found to neutralize prototype I653514 as well as the currently circulating strain 148974. In silico antigen-antibody interaction studies using molecular docking of predicted structures of NAbC and G-proteins of various CHPV strains led to the identifcation of a conserved neutralizing epitope in the fusion domain of G-protein, which also contained a putative T-helper peptide. The identifcation of a conserved neutralizing epitope in domain IV (fusion domain amino acids 53 to 172) of CHPV G-protein is an important fnding that may have the scope towards the development of protective targets against CHPV infection. Introduction Taxonomically, Chandipura virus (CHPV) belongs to the Vesiculovirus genus of the Rhabdoviridae family. CHPV causes acute encephalitis in human paediatric populations [1]. This virus was responsible for encephalitis outbreaks reported in Andhra Pradesh/Telengana and Maharashtra, India during the years 2003 and 2004 respectively [1, 2]. It is a negative sense, single stranded RNA virus which consists of fve structural proteins in the canonical order N-P-M-G- L: a nucleoprotein (N), a nucleocapsid-associated phospho- protein (P), a matrix protein (M), a glycoprotein (G) and the viral polymerase (RdRp, L) located between 3’ leader and 5’ trailer sequences. The G-protein is a trimeric trans-membrane glycoprotein that enables virus adsorption, assembly, budding and also elicits an antibody response thus acting as a major antigenic determinant [3]. Depending on the state of infection it adopts diferent reversible conformational states: i) native state pre- sent on the virus surface and stable above pH 7.0 [4] ii) activated state that fuses with the target membrane [5] iii) A fusion inactive post-fusion state which is stable under low pH conditions [6]. In earlier studies, the structure of a pre- fusion form of vesicular stomatitis virus (VSV) G-protein was analysed by the molecular replacement of diferent domains. The G-protein was divided into diferent domains, domain I: Lateral domain (1 to 17 and 310 to 382), domain II: Trimerization domain (18 to 35, 259 to 309, and 383 to 405), domain III: PH domain (36 to 46 and 181 to 258), domain IV: Fusion domain (53 to 172), Cter C-terminal part (406 to 413) and RbI-II domain: Rigid block (1 to 25 and 273 to 382) [7]. Being the major antigenic determinant, the G-protein of CHPV requires in depth studies to better understand its potential as a target for diferent preventive and diagnostic approaches. The emergence of massive CHPV outbreaks in 2003 with case fatality rates as high as 56-75 % [2] as well as isolated outbreaks thereafter from newer geographical Handling Editor: William G Dundon. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00705-018-3987-3) contains supplementary material, which is available to authorized users. * Pratip Shil shil.p@gov.in; shilpratip@gmail.com 1 ICMR-National Institute of Virology, 130/1 Sus Road, Pashan, Pune 411021, India