Porcine reproductive and respiratory syndrome virus counteracts the porcine intrinsic virus restriction factors-IFITM1 and Tetherin in MARC-145 cells

Porcine reproductive and respiratory syndrome virus (PRRSV) has been recognized to modulate the innate immune response of host. However, little is known about the effects of PRRSV infection on porcine intrinsic virus-restriction factors. This study presents the first demonstration that the nonstructural protein 3 (Nsp3) or envelope (E) protein of PRRSV interacted with porcine intrinsic virus-restriction factor IFITM1 or Tetherin. Next, in PRRSV-infected MARC-145 cells and the transfected cells with the IFITM1- or Tetherin-expressing plasmid, IFITM1 was shown to be mainly distributed perinuclear, and Tetherin was proposed to be partially removed away from cell surface. Moreover, the overexpression of IFITM1 and Tetherin were shown to have no obvious effects on the replication of PRRSV in MARC-145 cells. The Nsp3 of PRRSV was demonstrated to induce the proteasome-dependent degradation of IFITM1 upon PRRSV infection. These findings suggest that PRRSV might counteract the antiviral functions of IFITM1 and Tetherin by the interaction of the Nsp3 with IFITM1 and the E protein with Tetherin, providing a novel clue for exploring possible mechanisms associated with the evasion of PRRSV from immune recognition of host.