Of Mice and Men and Cattle: Functions of the Pneumovirus Nonstructural Proteins NS1 and NS2 in Interferon Escape

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