Characterization of the fusion core in zebrafish endogenous retroviral envelope protein

Abstract

Zebrafish endogenous retrovirus (ZFERV) is the unique endogenous retrovirus in zebrafish, as yet, containing intact open reading frames of its envelope protein gene in zebrafish genome. Similarly, several envelope proteins of endogenous retroviruses in human and other mammalian animal genomes (such as syncytin-1 and 2 in human, syncytin-A and B in mouse) were identified and shown to be functional in induction of cell-cell fusion involved in placental development. ZFERV envelope protein (Env) gene appears to be also functional in vivo because it is expressible. After sequence alignment, we found ZFERV Env shares similar structural profiles with syncytin and other type I viral envelopes, especially in the regions of N- and C-terminal heptad repeats (NHR and CHR) which were crucial for membrane fusion. We expressed the regions of N + C protein in the ZFERV Env (residues 459-567, including predicted NHR and CHR) to characterize the fusion core structure. We found N + C protein could form a stable coiled-coil trimer that consists of three helical NHR regions forming a central trimeric core, and three helical CHR regions packing into the grooves on the surface of the central core. The structural characterization of the fusion core revealed the possible mechanism of fusion mediated by ZFERV Env. These results gave comprehensive explanation of how the ancient virus infects the zebrafish and integrates into the genome million years ago, and showed a rational clue for discovery of physiological significance (e.g., medicate cell-cell fusion).

Mapping the m1A, m5C, m6A and m7G methylation atlas in zebrafish brain under hypoxic conditions by MeRIP-seq

“…In recent studies, we found that zebrafish endogenous retrovirus (ZFERV) has an envelope protein gene that maintains a complete open reading frame. This protein is highly expressed in the thymus of zebrafish and has a certain degree of presence in other organizations [ 57 , 58 ]. After exposure to hypoxia, the zebrafish repeat element expression regulation state, especially SSU-rRNA (Hsa), is changed.…”

Endogenous Retroviruses in Fish Genomes: From Relics of Past Infections to Evolutionary Innovations?

“…ZFERV is amplified in zebrafish T-cell leukemia ( Frazer et al, 2012 ). The fusion core of the ZFERV envelope protein has been characterized at the functional level ( Shi et al, 2015 ). In addition to ZFERV-related elements, we could detect two additional families of Epsilon-like sequences in the zebrafish genome that clearly segregate in a phylogeny, indicating the presence of divergent ERVs in this fish ( Figure 2 ).…”

Evolution and Genetic Diversity of the Retroviral Envelope in Anamniotes

“…Although a substantial number of RVs-GTE (retroviruses with a gamma-type Env) have been identified across the evolutionary history of vertebrates [15,[17][18][19], these retroviruses in anamniote vertebrates remain poorly understood. Hence, in this study, .…”

“…Although a substantial number of RVs-GTE (retroviruses with a gamma-type Env) have been identified across the evolutionary history of vertebrates [15,[17][18][19], these retroviruses in anamniote vertebrates remain poorly understood. Hence, in this study, by incorporating genomic and transcriptomic data and performing comprehensive phylogenomic analyses, we were able to identify hundreds of RV-GTE lineages, which significantly increased the known set of RVs-GTE in anamniote vertebrates.…”