Modulation of innate immune signaling by nonstructural protein 1 (nsp1) in the family Arteriviridae

Arteriviruses infect immune cells and may cause persistence in infected hosts. Inefficient induction of proinflammatory cytokines and type I IFNs are observed during infection of this group of viruses, suggesting that they may have evolved to escape the host immune surveillance for efficient survival. Recent studies have identified viral proteins regulating the innate immune signaling, and among these, nsp1 (nonstructural protein 1) is the most potent IFN antagonist. For porcine reproductive and respiratory syndrome virus (PRRSV), individual subunits (nsp1 alpha and nsp1 beta)of nsp1 suppress type I IFN production. In particular, PRRSV-nsp1 alpha degrades CREB (cyclic AMP responsive element binding)-binding protein (CBP), a key component of the IFN enhanceosome, whereas PRRSV-nsp1 beta degrades karyopherin-alpha 1 which is known to mediate the nuclear import of ISGF3 (interferon-stimulated gene factor 3). All individual subunits of nsp1 of PRRSV, equine arteritis virus (EAV), lactate dehydrogenase-elevating virus (LDV), and simian hemorrhagic fever virus (SHFV) appear to contain IFN suppressive activities. As with PRRSV-nsp1 alpha, CBP degradation is evident by LDV-nsp1 alpha and partly by SHFV-nsp1 gamma. This review summarizes the biogenesis and the role of individual subunits of nsp1 of arteriviruses for innate immune modulation. (C) 2014 Elsevier B.V. All rights reserved.