Structure & Capsids

1. Why Symmetry?

Crick & Watson’s 1956 insight: a virus genome is too small to encode many different shell proteins. The minimum-information solution is a single (or few) proteins assembled in symmetric arrays. Two solutions appear repeatedly: the helical rod of TMV-style viruses and the icosahedral shell of nearly every spherical virus. Both are derivable from the principle of equivalent environments for each subunit — the basis of self-assembly.

2. Helical Capsids: TMV

Tobacco mosaic virus is the prototype: ~2130 identical 158-residue coat protein subunits wind around a central RNA in a right-handed helix, 16.34 subunits per turn, pitch 23 Å, total length 300 nm. The RNA threads through the inner groove, with each subunit binding 3 nucleotides. Assembly is nucleated by an origin-of-assembly stem-loop in the RNA and proceeds by addition of two-layer disks.

Helical capsids work for any genome length — the helix simply gets longer. Filamentous bacteriophages (M13, fd) and many plant and animal viruses adopt this architecture. Influenza nucleocapsids are also helical inside their lipid envelope.

3. Icosahedral Capsids and the Caspar–Klug T-Number

An icosahedron has 20 triangular faces, 12 vertices, 30 edges, and three rotational symmetry axes (5-fold, 3-fold, 2-fold). The simplest icosahedral capsid has 60 identical subunits in equivalent environments — one per asymmetric unit. But 60 is too few subunits to enclose a useful genome.

In 1962 Donald Caspar & Aaron Klug (Nobel 1982) showed how more subunits could be incorporated while preserving near-equivalence. The trick is the triangulation number: \( T = h^2 + hk + k^2 \) for non-negative integers \(h, k\). The capsid contains \(60T\) subunits arranged in \(T\) quasi-equivalent positions per asymmetric unit.

• \(T = 1\) (60 subunits): parvoviruses, satellite tobacco mosaic virus.
• \(T = 3\) (180 subunits): poliovirus, picornaviruses, many plant viruses.
• \(T = 4\) (240): Sindbis virus, alphaviruses.
• \(T = 7\) (420): polyomavirus, papillomavirus, herpes nucleocapsid.
• \(T = 13\) or higher: rotavirus, reovirus, large dsDNA phages.

4. Enveloped Viruses

Many viruses wrap their nucleocapsid in a host-derived lipid bilayer studded with viral glycoproteins. Influenza, HIV, herpesviruses, coronaviruses, flaviviruses (dengue, Zika), and rhabdoviruses (rabies) are all enveloped. The envelope is acquired by budding through a host membrane — the plasma membrane in most cases, ER/Golgi for flaviviruses and coronaviruses, the inner nuclear membrane for herpes.

Envelope glycoproteins (HA on influenza, S/spike on coronaviruses, gp120 on HIV, E on dengue) mediate receptor binding and membrane fusion. They are the principal targets of neutralising antibodies and most vaccines. Envelopes make viruses fragile (sensitive to detergents, drying, lipid solvents) but flexible — they can deform and fuse.

5. Complex Capsids: T4 and the Tailed Phages

Bacteriophage T4 is neither pure helical nor pure icosahedral. It has a prolate icosahedral head (T = 13 with elongation), a contractile tail (helical), and fibrous baseplate appendages. The tail injects the dsDNA genome through the bacterial envelope by syringe-like contraction — a piece of nano-engineering we are still learning to copy. About 95% of phages in nature have this head-and-tail architecture (Caudovirales).

6. Giant Viruses

The 2003 discovery of mimivirus in cooling-tower amoebae upended size limits: 750 nm particle, 1.18 Mbp dsDNA genome, encoding 979 proteins including tRNAs and aminoacyl-tRNA synthetases — bigger than some bacteria. Subsequent giant viruses (pandoravirus, pithovirus,tupanvirus, medusavirus) reach 1500 nm and 2.5 Mbp. They blur the cellular/non-cellular distinction and have reignited debate about virus origins, with some authors proposing a fourth domain of life.