By simulating how viruses are capable of constructing their own protective protein coats, researchers reveal that linking several larger segments together may be better than building them piece-by-piece.

Genomic information is pretty important stuff, and if you’re a virus you really need to make sure it’s kept safe and sound. This is exactly what the capsid does.  These protective protein envelopes come in various shapes and sizes, and each are constructed during a process of replication known as self-assembly.

Each capsid is composed of many smaller subunits called capsomers, which act as individual building blocks in this 3D jigsaw puzzle. Construction of these puzzles has usually assumed that the bonds between each piece are fixed, and fit together in a stepwise fashion piece-by-piece.

However, with even the simplest viruses needing around 60 components to build a capsid, there are a huge number of different ways to achieve this. By using computer simulations to vary the strength of the bonds that occur when different numbers of subunits come together, a team led by Ulrich Schwarz from the University of Heidelberg has attempted to find out just what the best way is for a virus to complete this puzzle.

In their study, published today in BMC Biophysics, capsid construction was modelled under two different circumstances: one in which the bond strength is fixed and the coat assembles piece-by-piece (called direct assembly), and one in which the bond strength varies once a ring of five or six pieces have joined together – in which case they fuse and can only be joined with other similar ring-structures (called hierarchical assembly).

You can see just how these two mechanisms differ by watching these simulations (try playing both at the same time for a side-by-side comparison):

Direct Assembly (all bonds between capsomers are the same – blue colour):

Hierarchical Assembly (bond strength changes once a ring is formed – capsomers turn red):

The results of these simulations seem to suggest that while direct assembly processes may suit simple viruses, larger viruses with greater structural complexity favour a hierarchical scheme in which they are assembled more quickly.

Although this may not be apparent in the simulations above, Schwarz and his team explain that production of the final capsid is limited by the number of individual pieces in the puzzle. If only the exact number of pieces are available, fitting the final few slows things down—known a monomer starvation:

“In vivo, this constraint should be less relevant than in our simulations. Once a cell is infected by a virus, one expects to see a constant production rate for viral proteins, and therefore monomer starvation should be less of an issue.”

Future work on these real-world systems may therefore provide further clues to an even larger viral puzzle.