3.4 ENVELOPED (MEMBRANE-BOUND) VIRUS PARTICLES

Although they appear complex, these viruses have a conventional isometric or helical structure that is surrounded by a membrane – a 4-nm-thick lipid bilayer containing proteins. Examples include many of the larger animal viruses, but only a few plant and bacterial viruses. Traditionally these viruses were distinguished from nucleocapsid viruses by treatment with detergents or organic solvents, which disrupts the membrane and destroys infectivity. Thus they were sometimes referred to as “ether-sensitive viruses.” The envelope, which is derived from host cell membranes, is obtained by the virus budding from cell membranes, but most contain no cell proteins. How cell proteins are excluded and why retroviruses, the exception, do not exclude cell proteins from their virions are not understood (see Section 11.6). An isometric core surrounded by an isometric envelope: Sindbis virus particles Sindbis virus (a togavirus) has an icosahedral nucleocapsid that comprises a single protein, surrounded by an envelope from which viral spike Virion ISVP Core Inner capsid λ1, λ2, λ3, µ2, σ2 µ1, σ1, σ3 λ3 ⁄ µ2? λ3 ⁄ µ2? λ3 ⁄ µ2? λ1 ⁄σ2 λ1 ⁄σ2 λ1 ⁄σ2 µ1 µ1 µ1 µ1 σ3 σ3 λ2 λ2 λ2 λ2 λ2 λ2 σ1 σ1 ds RNA Outer capsid Fig. 3.12 The double capsid structure of reovirus showing the location of polypeptides in the virion. Here a section of the virion has been taken through the fivefold axis of symmetry of the vertex. In order to demonstrate protein function, two intermediates that occur during the virus uncoating process are also shown: the intermediate subviral particle (ISVP) and the viral core. In the ISVP, σ1 has achieved an extended conformation and σ3 has been lost from the outer capsid. Some molecules of σ1 may also be extended in the virion, but this is seen more frequently in the intermediate. The core is formed by the loss of the entire outer capsid and the change in conformation of the turret protein λ2 to form the channel through which mRNA synthesized in the particle will escape into the cell cytoplasm. (From M. L. Nibert et al. in B. N. Fields, D. M. Knipe and P. M. Howley eds., 1996 Virology, Lippincourt-Raven, p. 1562.) CHAPTER 3 THE STRUCTURE OF VIRUS PARTICLES 43 proteins protrude. The core has T = 3 and 180 subunits, exactly like tomato bushy stunt virus described above. Surprisingly, the envelope also has icosahedral symmetry, but to everyone’s surprise this is T = 4 and has 240 subunits. This apparent paradox was resolved when it was found that the two structures are complementary, so that the internal ends of the spike proteins fit exactly into depressions between the subunits of the nucleocapsid (Fig. 3.13). So far, this and its near relations are the only enveloped viruses that are known to have a geometrically symmetrical envelope. A helical core surrounded by an approximately spherical envelope: the influenza virus particle One of the best studied groups of enveloped viruses is the influenza viruses. The helical core is composed of the matrix (M1) protein surrounding a ribonucleoprotein, itself composed of a flexible rod of RNA and nucleoprotein (NP). This is constructed as described in Section 3.2, and arranged in a twisted hairpin structure. The genome is segmented RNA and there are eight separate core structures. Each is associated with a transcriptase complex. The core is contained within a lipid envelope that is only roughly spherical, and hence often described as pleomorphic (Fig. 3.13). M1 protein also lines the inner membrane surface. In electron micrographs (Fig. 3.14), a large number of protein spikes, projecting about 13.5 nm from the viral envelope, can be observed. These spikes, which have an overall length of 17.5 nm, are transmembrane glycoproteins like many of those in cell membranes. The spike layer consists solely of virus-specified glycoproteins, and comprises about 800 hemagglutinin (HA) and 200 neuraminidase (NA) proteins. HA proteins are trimers and NA proteins are tetramers. NA spikes are arranged nonrandomly in clusters on the virion surface. The HA functions in attachment and fusion-entry, and the NA releases infecting virus from receptors that do not lead to entry and infection. The NA also releases progeny virions which reattach to the host cell in which they were formed (see Section 5.1). Receptor analogs (e.g. Tamiflu) are antivirals that prevent virus release (see Section 21.8). The spikes are morphologically distinct. Figure 3.15 shows the structure of the influenza virus HA. Also in the membrane are a few molecules of an ion channel protein called M2. This allows the passage of protons into the core and is necessary for secondary uncoating