Virome analysis provides new insights into the pathogenesis mechanism and treatment of SLE disease.

Introduction: This study aimed to investigate the virome diversity of the SLE disease and the association between viral infections and the disease.

Methods: SLE-related RNA-Seq data were retrieved from public databases. A rigorous computational workflow was employed to identify the human viruses. Differential expression analysis and functional enrichment analysis were conducted in R.

Results: We identified ten human virus species from 826 RNA-Seq samples of human blood, comprising 688 SLE patients and 138 healthy controls. Eight of the ten virus species exhibited higher positive rates in SLE patients compared to healthy controls, with Human betaherpesvirus 5 (HHV5) having the highest positive rate (4.1%) and being exclusively detected in SLE samples. The virus abundances were low and comparable in both SLE patients and healthy controls. Analysis of the antiviral interferon-stimulated genes (ISGs) in samples showed higher ISG expression levels in HHV4 and HHV5-positive samples compared to virus-negative samples. Several genes that were up-regulated in SLE patients were further up-regulated after HHV5 infection, and they were mainly enriched in immune response-related biological processes. Additionally, the expression levels of several marker genes of SLE severity were compared between HHV5-positive and virus-negative SLE patients, suggesting that HHV5 infection may be associated with aggravated SLE disease.

Discussion: We found that SLE patients are more susceptible to viral infections than healthy individuals. Viral infections, such as HHV5, may be associated with aggravated SLE disease. This study deepens our understanding of the association between viruses and SLE and provides new insights into prevention and control of the disease.