|Nan, Yuchen -|
|Wang, Rong -|
|Shen, Meiyan -|
|Samal, Siba -|
|Zhang, Yan-Jin -|
Submitted to: Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 14, 2012
Publication Date: October 25, 2012
Citation: Nan, Y., Wang, R., Shen, M., Faaberg, K.S., Samal, S.K., Zhang, Y.J. 2012. Induction of type I interferons by a novel porcine reproductive and respiratory syndrome virus isolate. Virology. 432(2):261-270. Interpretive Summary: Porcine reproductive and respiratory syndrom virus (PRRSV) is the foremost disease of swine in the United States. In this report, a strain of virus was found to induce type 1 interferons in cells, different from other viral strains identified to date. The identification of this interferon-inducing PRRSV isolate might be beneficial for vaccine development to induce protective immunity against PRRS.
Technical Abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) inhibits synthesis of type I interferons (IFNs) in infected pigs and in cultured cells. Here we report that one PRRSV mutant A2MC2 induces type I IFNs in cultured cells and has no effect on IFN downstream signaling. The mutant isolate was propagated in a monkey kidney-derived cell line, MARC-145. Pre-treatment of Vero cells with culture supernatant from A2MC2-infected MARC-145 cells led to inhibition of LaSota Newcastle disease virus (NDV), an IFN-sensitive virus. The A2MC2 strain was confirmed to be Type 2 PRRSV by Western blotting with pig convalescent antiserum and by an inhibition assay with a PRRSV-specific antisense morpholino oligomer. A2MC2 replication in MARC-145 cells resulted in elevation of the transcripts of IFN-stimulated genes, ISG15 and ISG56, and the proteins of the signal transducer and activator of transcription (STAT) 2 and p56. A2MC2 infection of primary porcine pulmonary alveolar macrophages (PAMs) also led to elevation of STAT2 and p56, but little cytopathic effect. Furthermore, IFN signaling in either A2MC2-infected MARC-145 or PAM cells was not affected as no detectable decrease in the expression of the IFN-inducible genes was discovered in the cells that were treated with an external IFN-a, while other PRRSV strains, such as VR-2385, inhibit the expression of these genes. Sequencing analysis indicates that A2MC2 is closely related to VR-2332 and Ingelvac PRRS MLV. The identification of this IFN-inducing PRRSV isolate might be beneficial for vaccine development to induce protective immunity against PRRS.