A novel cause of chronic viral meningoencephalitis: Cache Valley virus

Wilson, Michael R.; Suan, Dan; Duggins, Andrew; Schubert, Ryan D.; Khan, Lillian M.; Sample, Hannah A.; Zorn, Kelsey C.; Rodrigues Hoffman, Aline; Blick, Anna; Shingde, Meena; DeRisi, Joseph L.

A total of 25,069,677 and 13,661,871 paired-end reads were obtained from the CSF and brain biopsy specimens, respectively. As described above, the paired-end sequences were processed through a custom bioinformatics pipeline. The runtime for the bioinformatics pipeline described above was 10 to 15 minutes per sample on a single 24core server. After filtering, there were 2 genera remaining in the mNGS dataset from the CSF sample: Bunyamwera virus (taxid: 35304) and cucumber green mottle mosaic virus (taxid: 12234). Only Bunyamwera virus was considered a credible pathogen. At the species level, the 5 unique pairs of Bunyamwera virus reads mapped to the CVV nucleoprotein and RNA-dependent RNA polymerase with 89 to 100% similarity. Although no Bunyamwera virus sequences were identified in the nt results from the brain biopsy sample, the nr output identified 2 unique read pairs that mapped with 99 to 100% similarity to the CVV S (small) genome segment that encodes the nucleocapsid protein and a nonstructural protein. Thus, the very simple and conservative algorithm described above resulted in a single taxonomic category (CVV) in our patient's CSF sample, which, upon further investigation, was also present in the brain biopsy sample. CVV is an orthobunyavirus known to cause acute neuroinvasive disease but not a chronic meningoencephalitis. CVV sequences have never been previously detected in this laboratory, nor have CVV reagents or materials been present in this laboratory. These nonhuman sequence reads corresponding to the libraries from this patient have been deposited at the NCBI Sequence Read Archive BioProject (PRJNA338853).