BINDING OF REOVIRUS TO RECEPTOR LEADS TO CONFORMATIONAL-CHANGES IN VIRAL CAPSID PROTEINS THAT ARE REVERSIBLE UPON VIRUS DETACHMENT

A conformational change was detected in reovirus upon its attachment t o mouse L fibroblasts. Specifically, the capsid proteins of cell-bound virions became more resistant to pepsin digestion. Similar observatio ns were made using glutaraldehyde-fixed cells or plasma membranes inst ead of live cells, indicating that virus internalization was not neces sary for this effect. This conformational change was totally reversibl e, since bound virions reverted back to the pepsin-sensitive state upo n release from the cell surface. Not unexpectedly, a conformational ch ange was also detected in the reovirus cell attachment protein sigma 1 when it alone bound to cells. The alteration was mapped, by deletion mutagenesis, to a region proximal to the N-terminal (virion-anchoring) end of the protein and was also found to be reversible. Structural ch anges in sigma 1 were also detectable following its interaction with s ialic acid (conjugated to bovine serum albumin) shown previously to be the minimal receptor determinant recognized by reovirus. These result s suggest that upon cell attachment, a signal is transmitted from the C-terminal receptor-binding region of sigma 1 to the N terminus in a r ipple-like progression that eventually leads to conformational changes in the other reovirus capsid proteins. An altered conformational stat e may be necessary for subsequent viral entry and programmed disassemb ly of viral capsids inside susceptible cells.