Abstract
Infection with the avian leukosis virus subgroup J (ALV-J) impairs host genes and facilitates the establishment of chronic infection and the viral life cycle. However, the involvement of long noncoding RNAs (lncRNAs) in ALV-J infection remains largely unknown. In this study, we identified a novel chicken lncRNA derived from LTR5B of the ERV-L family (namely lnc-LTR5B), which is significantly downregulated in ALV-J infected cells. lnc-LTR5B was localized in the cytoplasm and was relatively high expressed in the chicken lung and liver. Notably, the replication of ALV-J was inhibited by the overexpression of lnc-LTR5B but enhanced when lnc-LTR5B expression was knocked down. We further confirmed that lnc-LTR5B could bind to the binding immunoglobulin protein (BiP), a master regulator of endoplasmic reticulum (ER) function. Mechanistically, lnc-LTR5B serves as a competing endogenous RNA for BiP, restricting its physical availability. Upon ALV-J infection, the reduction of lnc-LTR5B released BiP, which facilitated its translocation to the cell surface. This is crucial for ALV-J entry as well as pro-survival signaling. In conclusion, we identified an endogenous retroviral LTR-activated lnc-LTR5B that is involved in regulating the cell surface translocation of BiP, and such regulatory machinery can be exploited by ALV-J to complete its life cycle and propagate.
Highlights
Avian leukosis virus (ALV), which belongs to the family Retrovirus, is an enveloped RNA virus that causes host immunosuppression and various tumors in chicken
To identify the host long noncoding RNAs (lncRNAs) involved in avian leukosis virus subgroup J (ALV-J) replication, we used RNA-seq to perform transcriptional analysis of CEF that were infected with ALV-J (JS09GY3 strain) or were mockinfected
Based on the idea that host lncRNAs targeted by viruses may participate in cellular antiviral responses, we focused on these downregulated lncRNAs during ALV-J infection
Summary
Avian leukosis virus (ALV), which belongs to the family Retrovirus, is an enveloped RNA virus that causes host immunosuppression and various tumors in chicken. The lack of understanding of the viral life cycles has hampered the development of specific antiviral drugs or effective vaccines against ALV-J. Successful ALV-J infection requires host factors at different stages of the viral life cycle. ALV-J infection begins with the viral envelope (Env) protein binding to its specific receptor NHE1 at the surface of host cells, followed by virion internalization (Chai and Bates, 2006; Guan et al, 2018). MiR-34b-5p, which is induced by ALV-J infection, targets melanoma differentiationassociated gene 5 (MDA5), which is a major cellular sensor for triggering type I interferon (Li et al, 2017). Screening more host factors targeted by ALV-J is beneficial to understand its pathogenic mechanisms and develop effective vaccines
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