An Endogenous Retroviral LTR-Derived Long Noncoding RNA lnc-LTR5B Interacts With BiP to Modulate ALV-J Replication in Chicken Cells

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.

Comparison of Endogenous Alpharetroviruses (ALV-like) across Galliform Species: New Distant Proviruses

“…The five species in the North American grouse clade (Clade IV) are phylogenetically close. If all the ERVs in this study were related, insertion is estimated to have happened 39.9 million years ago [ 62 , 63 ], or if only Phasianidae are considered and Callipepla and Colinus are excluded because they belong to a different phylogenetic branch (Family Odontophoridae), that estimate would be 35.2 to 42 million years ago [ 63 , 64 , 65 ]. This dating implies that an ancient retrovirus became endogenized in a common ancestor of the present Galliformes and underwent genetic drift with high levels of divergence in ERV genes among different families and subfamilies.…”

LncRNA LINC00534 regulates cell proliferation and migration via the miR‐494‐3p/PTEN axis in HTR‐8/SVneo cells

“…Potential bound proteins HS90A and HSP7C were reported to play roles in chaperones, but their roles in trophoblasts have not been proved. BiP (GRP78) was a master regulator of endoplasmic reticulum 49 . The status of BiP (GRP78) is associated with the invasive properties of cytotrophoblastic cells, syncytialisation and apoptosis in PE 50–52 .…”

“…BiP (GRP78) was a master regulator of endoplasmic reticulum. 49 The status of BiP (GRP78) is associated with the invasive properties of cytotrophoblastic cells, syncytialisation and apoptosis in PE. [50][51][52] Moreover, GRP78 is an upstream regulator of PI3K/AKT signaling, 53 while GRP78 has also been shown to be a downstream target of AKT.…”

Advances on genetic and genomic studies of ALV resistance

“…Not surprisingly, the immune effects of ERVs in poultry genes are contradictory. For example, a lncRNA (lnc-LTR5B) derived from ERV can regulating the cell surface translocation of BiP, which can be exploited by ALV-J to complete its life cycle [ 51 ]; while another lncRNA (lnc-ALVE1-AS1) can induce an antiviral innate immune response via a TLR3-dependent pathway in the cytoplasm [ 52 ].…”