Identification of potential molecular associations between chikungunya virus non-structural protein 2 and human host proteins
ACTA VIROLOGICA
Authors: Rana, J.; Gulati, S.; Rajasekharan, S.; Gupta, A.; Chaudhary, V.; Gupta, S.
Abstract
Chikungunya virus(CHIKV) non-structuralprotein 2 (nsP2) is considered to be the master regulator of viral RNA replication and host responses generated during viral infection. This protein has two main functional domains: an N-terminal domain which exhibits NTPase, RNA triphosphatase and helicase activities and a C-terminal protease domain. Understanding how CHIKV nsP2 interacts with its host proteins is essential for elucidating all the required processes for viral replication and pathogenesis along with the identification of potential targets for antiviral therapy. In current study yeast two-hybrid (Y2H) screening of a human fetal brain cDNA library was performed using nsP2 protein as bait. The analysis identified seven host proteins (CCDC130, CPNE6, POLR2C, MAPK9, EIF4A2, EEF1A1 and EIF3I) as putative interactors of CHIKV nsP2 which were selected for further analysis based on their roles in host cellular machinery. The gene ontology analysis indicates that these proteins are mainly involved in apoptosis, transcription and translational mechanism of host cell. Domain mapping of nsP2 revealed that these associations are not random connections but instead they have functional significance. Further studies to identify the amino acid residues and their chemical interactions that may help in opening new possibilities for preventing these interactions, thus reducing chances of chikungunya infection were performed. This study expands the understanding of CHIKV-host interactions and is important for rational approaches of discovering new antiviral agents.
Increased expression of copine VI in patients with refractory epilepsy and a rat model
JOURNAL OF THE NEUROLOGICAL SCIENCES
Authors: Zhu, Binglin; Zha, Jingsi; Long, Yan; Hu, Xiaotong; Chen, Guojun; Wang, Xuefeng
Abstract
Copine VI (CPNE6) is a member of copines family, a calcium-dependent phospholipids-binding protein group found in many diverse eukaryotic organisms. Although earlier studies have shown that CPNE6 is almost exclusively expressed in brain, the exact biological functions remain unclear. The purpose of this study is to explore the relationship between epilepsy and CPNE6 expression. In present study, we investigated the expression pattern and distribution of CPNE6 in patients with refractory epilepsy and in a chronic pilocarpine-induced epileptic rat model by quantitative real-time PCR, Western blot and immunofluorescence. The results showed that the expression of CPNE6 increased remarkably in epileptic patients and in experimental epileptic rats. Double immunofluorescence labeling studies have revealed that CPNE6 protein is mainly expressed in neurons, demonstrated by co-localization with the dendritic marker, MAP2. Our results are the first to indicate that the abnormal expression of the CPNE6 in epileptic brain tissue may play an important role in epilepsy, especially refractory epilepsy. (C) 2015 Elsevier B.V. All rights reserved.