New viral protein cage structures observed from in-vitro co-assembly experiments of oligonucleotides and brome mosaic virus coat proteins

Virus-like particles of many small viruses can form in vitro around a broad variety of non-cognate polyanionic cargo. While the reason for non-specific encapsulation in vitro is relatively well understood, how does a virus avoid production of virus-like particles that encapsulate many of the smaller, non-viral, transient RNAs and other polyions occurring in the cytoplasm, is still a puzzle. In attempting to answer this long-standing question we have studied the nature of chimeras which assemble out of small ssDNA oligonucleotides and viral coat protein. Through a combination of charge detection mass spectrometry and cryo-electron microscopy we have determined that co-assembling brome mosaic virus (BMV) coat proteins and nucleic acid oligomers results in capsid structures and stoichiometries that differ from the icosahedral virion. These previously unknown shell structures are strained and less stable than the native one. However, they contain large native structure fragments that could be recycled to form BMV virions, should a viral genome become available. The existence of such structures suggests the possibility of a previously unknown regulatory pathway for the packaging process inside cells.