The analysis of molecular characteristics and protein conformation prediction of Torque Teno Virus infecting from a lung transplant patient based on whole genome sequencing

Objective To investigate the genomic evolutionary characteristics and capsid protein conformational properties of Torque teno virus (TTV), and to analyze the molecular features of TTV in lung transplant recipients.Methods Bronchoalveolar lavage fluid (BALF) samples from severe H9N2 avian influenza case with a history of lung transplantation, serum samples from healthy individuals, and BALF samples from pneumonia patients were collected. Real-time quantitative PCR and probe-capture-based high-throughput sequencing were performed to construct a phylogenetic tree of TTV and model the three-dimensional structure of its capsid protein.Results Sequencing data analysis revealed that the logarithm of TTV read counts in BALF samples from lung transplant recipients was significantly higher than those from pneumonia patients without transplantation history and healthy controls (P<0.01 for both). Phylogenetic analysis indicated that the TTV strains from transplant recipients were closely related to TTV genotype 6, while strains from other sample types clustered into distinct evolutionary branches. Molecular modeling of the capsid protein identified a poorly conserved region (residues 283–309) in the transplant recipient-derived strain compared to the reference strain of the same genotype, leading to conformational alterations in the viral capsid.Conclusion Long-term immunosuppression post-lung transplantation may alter TTV replication dynamics, resulting in aberrant capsid protein synthesis and assembly, thereby inducing conformational changes that facilitate immune evasion. This mechanism may underlie the higher TTV viral loads observed in transplant recipients.