Discovery of a novel orthototivirus-like virus in patients with vulvovaginal candidiasis.

Introduction: Vulvovaginal candidiasis (VVC) is a common fungal infection affecting women worldwide. Although the vaginal microbiome has been extensively studied, the diversity of viruses present in the vaginal microenvironment remains poorly characterized. Methods: Vaginal swab samples from patients diagnosed with VVC were subjected to viral metagenomic sequencing using an Illumina NovaSeq platform. Viral contigs were assembled, annotated, and screened against public databases. Genome organization, pairwise sequence identity, and phylogenetic relationships were analyzed to determine the evolutionary position of the detected virus. Results: Here, we identified a novel double-stranded RNA virus, tentatively named Vaginal-associated orthototivirus-like 1 (VAOTV-1), in vaginal swab samples from patients with vulvovaginal candidiasis. VAOTV-1 was represented by a partial genome sequence of 4,332 bp, encoding a complete RNA-dependent RNA polymerase (RdRp; 729 amino acids) and a partial capsid protein (CP; 532 amino acids). The encoded RdRp protein shared a maximum amino acid sequence identity of 47.43% with Totiviridae sp. isolate 22AP502 (GenBank accession no. XTJ93729.1), reported from Bandicota indica. In contrast, the CP showed no significant similarity to any sequences currently available in public databases, and BLASTn searches against the NCBI nucleotide database did not yield any significant matches. Phylogenetic analysis, together with the relatively low amino acid sequence identity to known members of the genus Totivirus within the family Orthototiviridae, suggests that VAOTV-1 represents a distinct and highly divergent orthototivirus-like lineage. Discussion: These findings indicate that VAOTV-1 represents a highly divergent orthototivirus-like virus and expands the known diversity of totiviruses detected in human-associated mucosal environments. This discovery highlights previously unrecognized viral diversity in the vaginal virome and provides new insights into viruses associated with vulvovaginal candidiasis.