Principles of Virology. Jane Flint

Principles of Virology - Jane Flint


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      Internal proteins that contact the viral envelope are not embedded within the lipid bilayer but rather bind to its inner face. Such viral proteins are targeted to, and interact with, membranes by means of specific signals, which are described in more detail in Chapter 12.

      Virus particles that house large DNA genomes are structurally much more intricate than any considered in previous sections. Such particles comprise obviously distinct components with different symmetries and/or multiple layers and in some cases exhibit architectures that do not appear to be based on helical or icosahedral symmetry. In this section, we illustrate various ways in which multiple structural elements can be combined. As we shall see, some of these elements are dedicated to specific functions.

      DISCUSSION

       A virus particle with different structures in different hosts

      Throughout this chapter, we describe mature virus particles in terms of a single structure: “the” structure. However, it is important to appreciate that the architectures reported are those of particles isolated and examined under a single set of specific conditions, typically far from physiological. Structural studies of the flavivirus dengue virus, an important human pathogen, illustrate the conformational plasticity of some mature virus particles.

      The organization of the single dengue virus envelope glycoprotein, E, described in the text (Fig. 4.25) is that observed in particles propagated in cells of the mosquito vector maintained at 28°C. As noted previously, the E protein dimers are tightly packed and icosahedrally ordered. However, the epitopes for binding of antibodies that neutralize the virus at 37°C are either partially or entirely buried, suggesting that the virus particle might undergo temperature-dependent conformational transitions. Indeed, when particles are exposed to temperatures encountered in the mammalian host (e.g., 37°C), they do expand significantly, exposing segments of the underlying membrane, and the E protein interactions are altered (compare the left and right panels in the figure). In fact, particles exposed to higher temperatures are heterogeneous, and the example shown in the figure (right) represents but one of multiple forms, identified during selection of particles for three-dimensional reconstruction. Because a heterogeneous population of particles with less well-ordered E protein dimers represents the form of dengue virus recognized by the human immune system, these observations have important implications for the design of dengue virus vaccines.

image

      Structures of dengue virus particles at 28°C (left) and at ≥34°C (right), with the axes of five-, three-, and twofold rotational symmetry indicated by a pentagon, triangle, and ellipse, respectively. The E protein dimers that lie at the twofold axes are shown in gray and the other dimers with one subunit in green and one in cyan. The two oligosaccharides attached to each E protein monomer are indicated in red and yellow. The particles exposed to higher temperatures are characterized by exposed patches of membrane (purple) and significant reduction of dimer contacts at the threefold axes of icosahedral symmetry. Reprinted from Rey FA. 2013. Nature 497:443–444, with permission. Courtesy of F.A. Rey, Institut Pasteur.

       Fibriansah G, Ng TS, Kostyuchenko VA, Lee J, Lee S, Wang J, Lok SM. 2013. Structural changes in dengue virus when exposed to a temperature of 37°C. J Virol 87:7585–7592.

       Zhang X, Sheng J, Plevka P, Kuhn RJ, Diamond MS, Rossmann MG. 2013. Dengue structure differs at the temperatures of its human and mosquito hosts. Proc Natl Acad Sci U S A 110:6795–6799.

       Bacteriophage T4

      Bacteriophage T4, which has been studied for more than 50 years, is the classic example of an architecturally elaborate virus that contains distinct parts that exhibit icosahedral or helical symmetry. The T4 particle, which


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