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.

腮腺炎病毒（MuV）引起流行性腮腺炎。MuV还经常感染睾丸并诱发睾丸炎，睾丸炎是导致男性不育的重要病因。然而，MuV感染睾丸的潜在机制仍然未知。在这里，我们描述了唾液酸，AXL和MER受体酪氨酸激酶在小鼠主要睾丸细胞（包括Sertoli和Leydig细胞）中调节MuV的进入和复制。Sertoli和Leydig细胞中存在唾液酸，AXL和MER。唾液酸特异地介导MuV进入Sertoli和Leydig细胞，而AXL和MER都通过抑制细胞先天的抗病毒应答来促进MuV在细胞内的复制。从机理上讲，AXL和MER对1型干扰素信号的抑制对于在Sertoli和Leydig细胞中MuV复制至关重要。