Of Mice and Men and Cattle: Functions of the Pneumovirus Nonstructural Proteins NS1 and NS2 in Interferon Escape
b'Bovine respiratory syncytial virus (BRSV), family Paramyxoviridae, subfamily Pneumovirinae, is a major etiological agent of respiratory tract disease in calves. A peculiarity of pneumoviruses is the presence of two unique nonstructural protein genes, NS1 and NS2. We show that both BRSV NS proteins are necessary and sufficient to mediate IFN resistance. This function can also be transferred to another, unrelated virus, Rabies virus. The mechanism of IFN resistance is conserved among the Pneumovirinae since the NS proteins of human RSV (HRSV) and of Pneumoniavirus of Mice (PVM) are also able to mediate IFN resistance in a similar manner. Furthermore, both BRSV NS proteins are able to block the induction of IFN by inhibiting the activation of interferon regulatory factor 3 (IRF-3). As a result, BRSV is able to block the establishment of a cellular antiviral state. The characterization of interactions between virus (NS proteins) and the host cell (IFN system) will have important implications in the development of HRSV/BRSV vaccines'