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Review
. 2015 May:479-480:591-9.
doi: 10.1016/j.virol.2015.03.006. Epub 2015 Mar 19.

Adenovirus membrane penetration: Tickling the tail of a sleeping dragon

Christopher M Wiethoff  1 , Glen R Nemerow  2
Affiliations
Review

Adenovirus membrane penetration: Tickling the tail of a sleeping dragon

Christopher M Wiethoff et al. Virology. 2015 May.

Abstract

As is the case for nearly every viral pathogen, non-enveloped viruses (NEV) must maintain their integrity under potentially harsh environmental conditions while retaining the ability to undergo rapid disassembly at the right time and right place inside host cells. NEVs generally exist in this metastable state until they encounter key cellular stimuli such as membrane receptors, decreased intracellular pH, digestion by cellular proteases, or a combination of these factors. These stimuli trigger conformational changes in the viral capsid that exposes a sequestered membrane-perturbing protein. This protein subsequently modifies the cell membrane in such a way as to allow passage of the virion and accompanying nucleic acid payload into the cell cytoplasm. Different NEVs employ variations of this general pathway for cell entry (Moyer and Nemerow, 2011, Curr. Opin. Virol., 1, 44-49), however this review will focus on significant new knowledge obtained on cell entry by human adenovirus (HAdV).

Keywords: Adenovirus; Cell trafficking; Innate immunity; Membrane destruction; Protein VI; Receptors; Virus structure.

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Figures

Figure 1
Figure 1
Structure and organization of human adenovirus. (A) A schematic illustration of the organization of capsid and core proteins in human adenovirus. The locations of various proteins are represented by different-colored symbols and the corresponding names are shown (Right). The indicated locations of the core proteins are approximate. Shown in blue-colored lettering are the proteins whose structures have been identified in this study. (B) Overall organization of hexon and penton base subunits exhibiting pseudo-T = 25 icosahedral symmetry. Structurally unique hexons (1–4) are color-coded in light blue, pink, green, and khaki, respectively. Penton vertices are shown in magenta. Outer cement proteins IIIa and IX are shown in purple and blue, respectively. Fiber molecules associated with the penton base are disordered. The outline of the triangular icosahedral facet is shown as a gray triangle, whereas the border of the GON hexons is indicated by yellow-colored rope. (C) An exterior view of the triangular icosahedral facet that comprises 12 hexons along with penton base vertices shown in magenta. Color representations are the same as in B. (D) An interior view of the facet in C, with three minor proteins, V (green), VI (red), and VIII (orange). It is noteworthy that a copy of V, VI, and VIII forms a ternary complex beneath the vertices, whereas VIII (orange) molecules are arranged as staples along the border (yellow-colored rope) of the GON hexons. Reddy V S, and Nemerow G R. PNAS 2014;111:11715–11720
Figure 2
Figure 2
CryoEM structure of Ad12 complexed with a soluble recombinant form of integrin αvβ5. The structure is shown artistically as if one virion were interacting with a host cell in the foreground. A second Ad virion with modeled full-length fibers is shown in the distance. The cryoEM structure revealed a compact ring of integrin density over each penton base (yellow) with the RGD-loop (surface protrusions) spacing of the penton base promoting interaction between integrin heterodimers (red) (bottom). Segmented density regions corresponding roughly to individual integrin molecules are shown in solution on the lower left. Copyright American Society for Microbiology, Journal of Virology, Volume 73, Number 8, p. 6759–6768, cover image, 1999. G.R. Nemerow , L. Pache , V. Reddy , P.L. Stewart. Virology, Volume 384, Issue 2, 2009, 380 – 388
Figure 3
Figure 3
Interactions between protein VI and the PPHs. (A) A hybrid (surface and tube) representation illustrating associations mediated by one copy of VI (red tube) gluing the adjacent PPHs (1,1’) and connecting them to hexon-4’ arising from the neighboring GON tile. The cleaved propeptide of VI (purple tube) remains associated with PPH-1 inside the hexon cavity. Certain residues of VI are identified with blue-colored labels. The penton base (PB) is shown in magenta. (B) A close-up view of the propeptide (purple tube) interactions with PPH-1, shown as a gray ribbon. A few residues that are involved in propeptide (purple) and hexon (green) interactions are labeled. Names of hexon subunits (A and C) are shown in parentheses. Reddy V S, and Nemerow G R. PNAS 2014;111:11715–11720
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