ALV-J GP37 molecular analysis reveals novel virus-adapted sites and three tyrosine-based Env species

• Published in: PloS one Vol. 10; no. 4; p. e0122887
• Main Authors: Ye, Jianqiang, Fan, Zhonglei, Shang, Jianjun, Tian, Xiaoyan, Yang, Jialiang, Chen, Hongjun, Shao, Hongxia, Qin, Aijian
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 07.04.2015; Public Library of Science (PLoS)
• Subjects: Adaptation, Physiological; Amino Acid Motifs; Amino Acid Sequence; Avian leukosis; Avian Leukosis Virus - genetics; Avian Leukosis Virus - physiology; Cellular signal transduction; Comparative analysis; Gene Products, env - chemistry; Gene Products, env - genetics; Gene Products, env - metabolism; Hemangioma; Homology; Immunological diseases; Leukemia; Leukosis; Molecular modelling; Molecular Sequence Data; Mutation; Myeloid leukemia; Pathogenesis; Phenols (Class of compounds); Phylogeny; Poultry industry; Species; Transduction; Tumorigenesis; Tyrosine; Viral envelope proteins; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0122887

Compared to other avian leukosis viruses (ALV), ALV-J primarily induces myeloid leukemia and hemangioma and causes significant economic loss for the poultry industry. The ALV-J Env protein is hypothesized to be related to its unique pathogenesis. However, the molecular determinants of Env for ALV-J pathogenesis are unclear. In this study, we compared and analyzed GP37 of ALV-J Env and the EAV-HP sequence, which has high homology to that of ALV-J Env. Phylogenetic analysis revealed five groups of ALV-J GP37 and two novel ALV-J Envs with endemic GP85 and EAV-HP-like GP37. Furthermore, at least 15 virus-adapted mutations were detected in GP37 compared to the EAV-HP sequence. Further analysis demonstrated that three tyrosine-based motifs (YxxM, ITIM (immune tyrosine-based inhibitory motif) and ITAM-like (immune tyrosine-based active motif like)) associated with immune disease and oncogenesis were found in the cytoplasmic tail of GP37. Based on the potential function and distribution of these motifs in GP37, ALV-J Env was grouped into three species, inhibitory Env, bifunctional Env and active Env. Accordingly, 36.91%, 61.74% and 1.34% of ALV-J Env sequences from GenBank are classified as inhibitory, bifunctional and active Env, respectively. Additionally, the Env of the ALV-J prototype strain, HPRS-103, and 17 of 18 EAV-HP sequences belong to the inhibitory Env. And models for signal transduction of the three ALV-J Env species were predicted. Our findings and models provide novel insights for identifying the roles and molecular mechanism of ALV-J Env in the unique pathogenesis of ALV-J.