A tombus-like virus in patients with lower respiratory tract infection: an observational study based on meta-transcriptomic sequencing.

The identification of a novel virus related to the family Tombusviridae, provisionally named human tombus-like virus (hTLV), is significant in the context of ongoing surveillance for respiratory pathogens. Meta-transcriptomic sequencing was utilized to detect respiratory pathogens in patients with lower respiratory tract infections (LRIs) in Jinan, China, from 2022 to 2023. The additional hTLV infections were identified through retrospective analysis of meta-transcriptome data collected in Beijing, China, from 2016 to 2019, prior to the COVID-19 outbreak. Phylogenetic analyzes indicated that hTLVs were clustered with a Jingmen tombus-like virus 2 but in a distinct clade. The hTLVs genomes consist of a single-stranded positive-sense RNA genomes of 4.7-4.8 kb in size, and contained four putative open reading frames (ORF1-4). The RNA-dependent RNA polymerase protein of hTLV shared significant sequence similarity containing three conserved motifs with 15, 24, and 15 amino acids, respectively. The hTLV genome included the canonical Gly376-Asp377-Asp378 (GDD) catalytic residues, which were a unifying feature of viruses in the family Tombusviridae. The main clinical manifestations of the 23 patients were fever, cough, expectoration and dyspnea, with varying degrees of lung infection or abnormalities in other laboratory indicators. Serological studies showed that fourfold rise in IgG titers in sera of a patient between acute and convalescent phase by ELISA. Identification of the pathogens for acute respiratory tract infections is essential for timely public health interventions and clinical management. The discovery of a novel virus, hTLV, in patients with LRIs highlights the continuous emergence of new respiratory pathogens in humans.