Porcine Mx proteins inhibit pseudorabies virus replication through interfering with early gene synthesis

Pseudorabies virus (PRV) is an enveloped, linear double-stranded DNA herpesvirus that resulted in huge financial losses to the swine industry. In addition to vaccination, the development of antiviral molecules is also a beneficial supplement to the control of Pseudorabies (PR). Although our previous studies have shown that porcine Mx protein (poMx1/2) significantly inhibited the proliferation of RNA virus, it was unknown whether poMx1/2 could inhibit porcine DNA virus, such as PRV. In this study, it was investigated the inhibitory effect of porcine Mx1/2 protein on PRV multiplication. The results showed that both poMx1 and poMx2 had anti-PRV activities, which required GTPase ability and stable oligomerization. Interestingly, the two GTPase deficient mutants (G52Q and T148A) of poMx2 also had the antiviral ability against PRV, which was consistent with previous reports, indicating that these mutants recognized and blocked the viral targets. Mechanistically, the antiviral restriction of poMx1/2 came from their inhibition of the early gene synthesis of PRV. Our results for the first time shed light on the antiviral activities of two poMx proteins against DNA virus. The data from this study provide further insights to develop new strategies for preventing and controlling the diseases caused by PRV.