Metagenomic Discovery and Characterization of OVRE1: A Chimeric Viral-Retroviral Pathogen in Human Gut and Vaginal Niches Associated with Unexplained Chronic Neuro-Gut Inflammation

Discovery of OVRE1 This study describes a female patient with chronic unexplained inflammation affecting both the gut and the vaginal mucosa, in whom routine microbiological and serological testing failed to identify a clear etiological agent. Metagenomic sequencing of gut and vaginal samples was performed on stringently host-depleted DNA and RNA, followed by PFAM domain annotation of the microbial metagenome. A rich landscape of retroviral, viral, and mobile genetic element–associated domains was detected at both sites, including MLV-like and BIV-like motifs (MLVIN_C, BIV_Env), reverse transcriptase RVT_1, integrase cores (rve, phage integrase families), retroviral capsid proteins (Gag_p24/p30), zinc-finger modules (zf‑C2H2/UBZ), and recurrent uncharacterized domains (DUF16, DUF2203). Quantitative analysis showed that these domains are enriched relative to the total predicted proteome in both gut and vaginal metagenomes, with higher overall enrichment of integrase, zinc-finger, and DUF families in the gut, and a more compact retroviral-like cassette in the vaginal niche. Gene-neighborhood analysis and a scaffold-level PFAM aggregation file (M_GUT_DNA_20M_targeted_scaffold_summary.tsv) revealed contigs in the vaginal dataset—most prominently scaffold k119_12088—where Gag, RT, integrase, and Env-like domains co-occur with herpes-like, pox-like, viroporin, toxin, and CobW-like metabolic genes in a single multi-kilobase unit, consistent with a near-complete MLV/BIV-like retroviral chassis expanded by additional virulence and metabolic modules, here provisionally designated OVRE1. Importantly, the same OVRE1-defining chimeric junctions and PFAM-domain combinations were also detected in the spouse’s gut metagenome, reconstructed with comparable coverage and junction-spanning read support, indicating that OVRE1 represents a shared, horizontally transmissible element rather than an idiosyncratic assembly confined to a single host. These findings support the presence of a shared MLV/BIV-based retro/mobile genetic “background” across the gut–vaginal axis at the household level that may contribute to chronic mucosal inflammation and motivate the development of PFAM-based diagnostic panels for patients with unexplained inflammatory syndromes.