Principles of Virology. Jane Flint

Principles of Virology - Jane Flint


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with icosahedral symmetry, the positions of pentamers determine the geometry of cones. However, in cones, pentamers are present only in the terminal caps. The human immunodeficiency virus type 1 cones formed in vitro and isolated from mature virions can be modeled as a fullerene cone assembling on a curved hexagonal lattice with five pentamers (red) at the narrow end of the cone, as shown in the expanded view. The wide end would be closed by an additional 7 pentamers (because 12 pentamers are required to form a closed structure from a hexagonal lattice). (C) The fullerene cone model was subsequently confirmed and refined by cryo-EM of helical tubes of CA at higher resolution, molecular dynamics simulations, and cryo-EM of cores purified from and within virus particles. Shown is an example of computational slices of perfect fullerene cones observed within virus particles, with cryoelectron tomographic models superimposed. The C-terminal domains of CA molecules are shown in gray, the N-terminal domains of CA pentamers in blue, and those of CA hexamers colored according to the quality of their alignment, from red (low) to green (high). From Mattei S. 2017. Science 354:1434–1437, with permission. Courtesy of J. Briggs, European Molecular Biology Laboratory, Heidelberg, Germany.

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       Li S, Hill CP, Sundquist WI, Finch JT. 2000. Image reconstructions of helical assemblies of the HIV-1 CA protein. Nature 407:409–413.

       Zhao G, Perilla JR, Yufenyuy EL, Meng X, Chen B, Ning J, Ahn J, Gronenborn AM, Schulten K, Aiken C, Zhang P. 2013. Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics. Nature 497:643–646.

       Mattei S, Glass B, Hagen WJH, Kräusslich H-G, Briggs JAG. 2016. The structure and flexibility of conical HIV-1 capsids determined within intact virions. Science 354:1434–1437.

      A definitive property of a virion is the presence of a nucleic acid genome. Incorporation of the genome requires its discrimination from a large population of cellular nucleic acid. This packaging process is described in Chapter 13. The volumes of closed capsids are finite. Consequently, accommodation of viral genomes necessitates a high degree of condensation and compaction. A simple analogy illustrates vividly the scale of this problem; packing of the ~150-kbp DNA genome of herpes simplex virus type 1 into the viral capsid is equivalent to stuffing some 10 ft of 22 American gauge wire (diameter, 0.644 mm) into a tennis ball. Such confinement of the genome can result in high internal pressure, equivalent to that generated in locomotive steam engines, some 18 and 25 atm within herpes simplex virus type 1 and phage capsids, respectively. Such pressure provides the force that powers ejection of DNA genomes. Packaging of nucleic acids is an intrinsically unfavorable process because of the highly constrained conformation imposed on the genome. In some cases, the force required to achieve packaging is provided, at least in part, by specialized viral proteins that harness the energy released by hydrolysis of ATP to drive the insertion of DNA. In many others, the binding of viral RNA or DNA genomes to capsid proteins appears to provide sufficient energy. The latter interactions also help to neutralize the negative charge of the sugar-phosphate backbone, a prerequisite for close juxtaposition of genome sequences.

      We possess relatively little information about the organization of genomes within viral particles: nucleic acids or protein-nucleic acid assemblies are not visible in the majority of high-resolution structural studies reported. This limitation indicates that the genomes or internal structures lack the symmetry of the capsid, do not adopt the same conformation in every viral particle, or both. Nevertheless, three mechanisms for condensing and organizing nucleic acid molecules within capsids can be distinguished and are described in the following sections.

      Use of the same protein or proteins both to condense the genome and to build a capsid allows efficient utilization of limited genetic capacity. It is therefore an advantageous arrangement for viruses with small genomes. However, this mode of genome packing is also characteristic of some larger viruses, notably rotaviruses and herpesviruses. The genome of rotaviruses comprises 11 segments of double-stranded RNA located within the innermost of the three protein shells of the particle. Remarkably, as much as 80% of the RNA genome appears highly ordered within the core, with strong elements of icosahedral symmetry (Fig. 4.19B).


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