Porcine Reproductive and Respiratory Syndrome Virus Inhibits Type I Interferon Signaling by Blocking STAT1/STAT2 Nuclear Translocation

• DOI: 10.1128/jvi.00655-10
• Publication Date: 2010-08-26T01:52:55Z
• Authors: Deendayal Patel; Yuchen Nan; Meiyan Shen; Krit Ritthipichai; Xiaoping Zhu; Yan-Jin Zhang
• Keywords: STAT2; ISG15; STAT1; Interferon type I

ABSTRACT Type I interferons (IFNs) IFN-α/β play an important role in innate immunity against viral infections by inducing antiviral responses. Porcine reproductive and respiratory syndrome virus (PRRSV) inhibits the synthesis of type IFNs. However, whether PRRSV can inhibit IFN signaling is less well understood. In present study, we found that interferes with pathway. The transcript levels IFN-stimulated genes ISG15 ISG56 protein level signal transducer activator transcription 2 (STAT2) VR2385-infected MARC-145 cells were significantly lower than those mock-infected after IFN-α treatment. IFN-induced phosphorylation both STAT1 STAT2 their heterodimer formation PRRSV-infected not affected. majority STAT1/STAT2/IRF9 (IFN regulatory factor 9) heterotrimers remained cytoplasm cells, which indicates nuclear translocation was blocked. Overexpression NSP1β VR2385 inhibited expression blocked STAT1, suggests might be responsible for inhibition signaling. infection primary porcine pulmonary alveolar macrophages (PAMs) also IFN-α-stimulated ISGs protein. contrast, a licensed low-virulence vaccine strain, Ingelvac PRRS modified live (MLV), activated IFN-inducible genes, including chemokines proteins, PAMs without addition external had no detectable effect on These findings suggest activation pathway IFNs blocking ISG 3 (ISGF3) translocation.