HEV infection aggravates testicular damage via inhibition of UBR2-mediated ubiquitination in the testis (PRJCA038157)
Hepatitis E virus (HEV) infection in the testis is associated with oligospermia and infertility. However, the underlying pathogenesis mechanism remains unclear. In this study, HEV-infected animal models were used, and single-cell RNA sequencing was performed to assess the influence of HEV infection on the testis. The number of spermatogonia, round spermatids and elongated spermatids markedly decreased upon infection. Ubiquitin protein ligase E3 component N-recognin 2 (UBR2), which is highly expressed in the testis and plays an essential role in spermatogenesis, was significantly downregulated in HEV-infected semen and testes. HEV infection significantly inhibited UBR2-mediated ubiquitination. Treatment with CC-5013, an activator of ubiquitination, restored normal sperm morphology and attenuated testicular damage. The results demonstrated that HEV infection inhibits UBR2-mediated ubiquitination and impairs sperm function. Furthermore, HEV infection activates M1 macrophages and promotes apoptosis. In summary, the loss of UBR2 impairs spermatogenesis and exacerbates testicular damage, which may lead to oligospermia or infertility.