Читать книгу Principles of Virology - Jane Flint, S. Jane Flint - Страница 201

Members of the Herpesviridae exhibit a number of unusual architectural features. More than half of the >80 genes of herpes simplex virus type 1 encode proteins found in the large (~200-nm-diameter) virus particles. These proteins are components of the envelope from which glycoprotein spikes project or of two distinct internal structures. The latter are the nucleocapsid surrounding the DNA genome and the protein-aceous layer encasing this structure, called the tegument (Fig. 4.27A). Until recently we possessed only relatively low-resolution views (at best, ~7 Å) of herpesviral particles. Technical advances in cryo-EM image reconstruction, including relaxation of icosahedral symmetry restraints, produced high-resolution structures of herpes simplex virus type 1 and type 2 particles (3.2 to 3.5 Å), by far the largest virus particles to be visualized in such detail. These remarkable achievements confirmed architectural elements of the nucleocapsid shared with smaller virus particles, but also revealed new features.

A single protein (VP5) forms both the hexons and the pentons of the T = 16 icosahedral capsid of herpes simplex virus type 1 (Fig. 4.27B). Like the structural units of the smaller simian virus 40 capsid, these VP5-containing assemblies make direct contact with one another. However, the segments of VP5 subunits that form the nucleocapsid floor adopt quite different conformations in the pentons and hexons (Fig. 4.27B). Similarly, specific VP5 regions display distinct arrangements in hexons that abut pentons and those surrounded entirely by other hexons. These differences optimize interactions among the structural units. The large herpesviral capsid, like that of adenoviruses, is further stabilized by additional proteins, including two that form triplexes that link the major structural units. A second property shared with polyomaviruses (and papillomaviruses) is stabilization of the particle by disulfide bonds, which covalently link both subunits of the triplexes and triplexes to VP5 subunits of adjacent hexons to impart rigidity. Such a network of covalent bonds must greatly increase the stability of the large nucleocapsid and may also be necessary to counter the high pressure exerted on this protein shell (see “Mechanical Properties of Virus Particles”).

Figure 4.26 Morphological complexity of bacteriophage T4. (A) A model of the virus particle. (B) Structure of the head (22-Å resolution) determined by cryo-EM, with the major capsid proteins shown in blue (gp23*) and magenta (gp24*), the protein that protrudes from the capsid surface in yellow, the protein that binds between gp23* subunits in white, and the beginning of the tail in green. Reprinted from Fokine A et al. 2004. Proc Natl Acad Sci U S A 101:6003–6008, with permission. Courtesy of M. Rossmann, Purdue University.

Although apparently a typical and quite simple icosahedral shell, this viral capsid is in fact an asymmetric structure: 1 of the 12 vertices is occupied not by a VP5 penton but by a unique structure termed the portal. The portal comprises 12 copies of the UL6 protein and is a squat, hollow cylinder that is wider at one end and surrounded by a two-tiered ring at the wider end (Fig. 4.27C). The incorporation of the portal, which is connected to the viral membrane (Fig. 4.27D), has important implications for the mechanism of assembly and delivery of viral genomes during entry (see Chapters 13 and 5).

The tegument contains >20 viral proteins, viral RNAs, and cellular components. A few tegument proteins are icosahedrally ordered, as a result of direct contacts with the structural units of the capsid. For example, three tegument proteins form a distinctive structure that caps the pentons and buttresses their association with neighboring triplexes. Tegument proteins are not uniformly distributed around the capsid, but are concentrated on one side, where they form a well-defined cap-like structure (Fig. 4.27A). The connection of the portal vertex of the capsid to the viral membrane (Fig. 4.27D) seems likely to account for this asymmetry.