Abstract
Mumps virus (MuV) infection has high tropism to the testis and usually leads to orchitis, an etiological factor in male infertility. However, MuV replication in testicular cells and the cellular antiviral responses against MuV are not fully understood. The present study showed that MuV infected the majority of testicular cells, including Leydig cells (LC), testicular macrophages, Sertoli cells (SC), and male germ cells (GC). MuV was replicated at relatively high efficiencies in SC compared with LC and testicular macrophages. In contrast, MuV did not replicate in male GC. Notably, testicular cells exhibited different innate antiviral responses against MuV replication. We showed that interferon β (IFN-β) inhibited MuV replication in LC, macrophages, and SC, which were associated with the upregulation of major antiviral proteins. We provided primary evidence that autophagy plays a role in blocking MuV replication in male GC. Autophagy was also involved in limiting MuV replication in testicular macrophages but not in Leydig and SC. These findings indicate the involvement of the innate defense against MuV replication in testicular cells.
Highlights
Mumps virus (MuV) infection usually causes orchitis and may result in male infertility [1]
To examine MuV infection of testicular cells, including Leydig cells (LC), testicular macrophages, Sertoli cells (SC), and germ cells (GC) were isolated from 4-weekold C57BL/6 male mice
These findings suggest that MuV infects major testicular cells
Summary
Mumps virus (MuV) infection usually causes orchitis and may result in male infertility [1]. Mumps orchitis is associated with direct MuV infection in the testis. Understanding the innate antiviral response against MuV replication in testicular cells can aid in the development of therapeutic strategies for mumps orchitis. MuV infection may result in the inflammation of several other organs, including encephalitis, meningitis, myocarditis, pancreatitis, nephritis, and orchitis [3]. Mumps orchitis is the most common extra-salivary gland inflammation caused by MuV infection [4]. The recovery of MuV from the testis and the semen of mumps orchitis patients suggest that a direct MuV infection in the testis is associated with diseases [5, 6]. MuV infection and replication in testicular cells remain elusive
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