Pseudorabies virus inhibits progesterone-induced inactivation of TRPML1 to facilitate viral entry

• DOI: 10.1371/journal.ppat.1011956
• Publication Date: 2024-01-31T18:36:31Z
• Authors: Bing-Qian Su; Guo-Yu Yang; Jiang Wang; Sheng-Li Ming; Bei-Bei Chu
• Keywords: Pseudorabies

Viral infection is a significant risk factor for fertility issues. Here, we demonstrated that by neurotropic alphaherpesviruses, such as pseudorabies virus (PRV), could impair female disrupting the hypothalamus-pituitary-ovary axis (HPOA), reducing progesterone (P4) levels, and consequently lowering pregnancy rates. Our study revealed PRV exploited transient receptor potential mucolipin 1 (TRPML1) its lipid activator, phosphatidylinositol 3,5-bisphosphate (PI(3,5)P 2 ), to facilitate viral entry through lysosomal cholesterol Ca 2+ . P4 antagonized this process inducing storage disorders promoting proteasomal degradation of TRPML1 via murine double minute (MDM2)-mediated polyubiquitination. Overall, identifies novel mechanism which hijacks pathway evade P4-mediated antiviral defense fertility. This may be common among alphaherpesviruses contribute significantly their impact on reproductive health, providing new insights development therapies.