Abstract
The mumps virus (MuV) causes epidemic parotitis. MuV also frequently infects the testis and induces orchitis, an important etiological factor contributing to male infertility. However, mechanisms underlying MuV infection of the testis remain unknown. Here, we describe that sialic acid, AXL, and MER receptor tyrosine kinases regulate MuV entry and replication in mouse major testicular cells, including Sertoli and Leydig cells. Sialic acid, AXL, and MER were present in Sertoli and Leydig cells. Sialic acid specifically mediated MuV entry into Sertoli and Leydig cells, whereas both AXL and MER facilitated MuV replication within cells through the inhibition of cellular innate antiviral responses. Mechanistically, the inhibition of type 1 interferon signaling by AXL and MER is essential for MuV replication in Sertoli and Leydig cells. Our findings provide novel insights into the mechanisms behind MuV infection and replication in the testis.
Highlights
The mumps virus (MuV) is a pathogen that causes epidemic mumps, a painful parotitis (Latner and Hickman, 2015)
Relative MuV nuclear protein (MuV-NP) RNA levels were detected by real-time qRT-PCR in Sertoli and Leydig cells 1 h after incubation with different doses of MuV on ice for MuV binding (Figure 1B)
The results suggest that MuV can efficiently bind to Sertoli and Leydig cells, and that the bound MuV can be removed by trypsin treatment
Summary
The mumps virus (MuV) is a pathogen that causes epidemic mumps, a painful parotitis (Latner and Hickman, 2015). MuV has tropism for the testis, thereby frequently inducing orchitis, which may result in male infertility (Litman and Baum, 2010). MuV infection may result in inflammation in multiple other organs, Mumps Virus in the Testis including the central nervous system, pancreas, kidney, ovary, and testis (Rubin and Sauder, 2013). While mumps orchitis in childhood is self-limiting and rarely leads to sterility, MuV infection in post-pubertal men frequently results in chronic orchitis, one important etiological factor of male infertility. MuV triggers innate immune responses in mouse Sertoli and Leydig cells, thereby inducing the expression of pro-inflammatory cytokines and impairing testosterone synthesis (Wu et al, 2016). MuV infection of Sertoli cells impairs the integrity of the blood-testis barrier through the induction of TNFA (Wu et al, 2019). While MuV infects testicular cells and impairs testicular functions, the mechanisms underlying MuV infection and replication in the testicular cells remain to be elucidated
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