3′UTR of ALV-J can affect viral replication through promoting transcription and mRNA nuclear export
Moru Xu, Kun Qian, Hongxia Shao, Yongxiu Yao, Venugopal Nair, Jianqiang Ye, Aijian Qin
Abstract
ABSTRACT 3′ Untranslated regions (3′UTRs) play a crucial role in gene transcription and post-transcriptional regulation. During the past 30 years, subgroup J avian leukosis virus (ALV-J) had accumulated large-scale mutations in 3′UTRs of their proviral genome. In this study, we summarize five kinds of mutant 3′UTRs in ALV-J and analyzed their potential functions. Results indicated that ALV-J strains containing different 3′UTRs showed different replication ability, while this divergence is tissue preferential, especially in chicken embryonic liver cells and chicken endothelial cells. All 3′UTRs can assist intron-containing viral mRNA nuclear export, with no salient differences among the five forms. The half-life of ALV-J mRNA is not influenced by different 3′UTRs. However, 3′UTRs can drastically boost mRNA transcription in a cell-specific manner. These different 3′UTRs can promote foreign genes expression. Our results provide novel insight into the pathogenicity and life cycle of ALV-J. IMPORTANCE 3′UTRs can affect gene transcription and post-transcriptional regulation in multiple ways, further influencing the function of proteins in a unique manner. Recently, ALV-J has been mutating and evolving rapidly, especially the 3′UTR of viral genome. Meanwhile, clinical symptoms caused by ALV-J have changed significantly. In this study, we found that the ALV-J strains containing △-r-TM-type 3′UTR are the most abundant. By constructing ALV-J infectious clones and subgenomic vectors containing different 3′UTRs, we prove that 3′UTRs directly affect viral tissue preference and can promote virus replication as an enhancer. ALV-J strain containing 3′UTR of △-r-TM proliferated fastest in primary cells. All five forms of 3′UTRs can assist intron-containing viral mRNA nuclear export, with similar efficiency. ALV-J mRNA half-life is not influenced by different 3′UTRs. Our results dissect the roles of 3′UTR on regulating viral replication and pathogenicity, providing novel insights into potential anti-viral strategies.