Principles of Virology. Jane Flint

A. 2013. Herpes virus genome, the pressure is on. J Am Chem Soc 135:11216–11221.

       The first experimental measurement of the high internal pressure within a human virus capsid.

      Caspar DL, Klug A. 1962. Physical principles in the construction of regular viruses. Cold Spring Harb Symp Quant Biol 27:1–24.

       Theoretical principles of quasiequivalence and triangulation number for construction of icosahedral virus particles.

      Crick FH, Watson JD. 1956. Structure of small viruses. Nature 177:473–475.

       The classic proposal that viruses are built from identical subunits (for genetic economy) arranged with helical or platonic polyhedral symmetry.

      Harrison SC, Olson AJ, Schutt CE, Winkler FK, Bricogne G. 1978. Tomato bushy stunt virus at 2.9 Å resolution. Nature 276:368–373.

       First X-ray crystal structure of an icosahedral virus and identification of the β-barrel jelly roll topology. Note the high resolution achieved even more than 40 years ago!

      Hogle JM, Chow M, Filman DJ. 1985. Three-dimensional structure of poliovirus at 2.9 Å resolution. Science 229:1358–1365.

      Rossmann MG, Arnold E, Erickson JW, Frankenberger EA, Griffith JP, Hecht H-J, Johnson JE, Kamer G, Luo M, Mosser AG, Rueckert RR, Sherry B, Vriend G. 1985. Structure of a human common cold virus and functional relationship to other picornaviruses. Nature 317:145–153.

       The first three-dimensional structures of human viruses.

      Liu H, Jin L, Koh SB, Atanasov I, Schein S, Wu L, Zhou ZH. 2010. Atomic structure of human adenovirus by cryo-EM reveals interactions among protein networks. Science 329:1038–1043.

       A milestone in cryo-EM of virus particles, a 3.6-Å resolution structure of human adenovirus type 5, a large virus particle that includes several stabilizing proteins.

      Mancini EJ, Clarke M, Gowen BE, Rutten T, Fuller SD. 2000. Cryo-electron microscopy reveals the functional organization of an enveloped virus, Semliki Forest virus. Mol Cell 5:255–266.

      This <10-Å resolution cryo-EM structure revealed the organization of transmembrane segments of the viral glycoproteins and contacts between the capsid and glycoproteins.

      Massiah MA, Starich MR, Paschall C, Summers MF, Christensen AM, Sundquist WI. 1994. Three-dimensional structure of the human immunodeficiency virus type 1 matrix protein. J Mol Biol 244:198–223.

       The first structure of an internal viral protein reported.

      Sharma M, Yi M, Dong H, Qin H, Peterson E, Busath DD, Zhou HX, Cross TA. 2010. Insight into the mechanism of the influenza A proton channel from a structure in a lipid bilayer. Science 330:509–512.

       Insights into the mechanism of action of a viroporin from structural biology.

      Twarock R, Luque A. 2019. Structural puzzles in virology solved with an over-arching icosahedral design principle. Nat Commun 10:4414.

       An important generalization and extension of the principle of quasiequivalence.

      Varnum SM, Streblow DN, Monroe ME, Smith P, Auberry KJ, Pasa-Tolic L, Wang D, Camp DG II, Rodland K, Wiley S, Britt W, Shenk T, Smith RD, Nelson JA. 2004. Identification of proteins in human cytomegalovirus (HCMV) particles: the HCMV proteome. J Virol 78:10960–10966.

       An early example of application of mass spectrometry to virus particles.

      Wilson IA, Skehel JJ, Wiley DC. 1981. Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 Å resolution. Nature 289: 366–373.

       X-ray crystal structure of the external domain of this glycoprotein, the first to be determined.

       Websites

      http://viperdb.scripps.edu/ Virus Particle Explorer

      http://viralzone.expasy.org/ ViralZone

      http://www.virology.net/Big_Virology/BVHomePage.html The Big Picture Book of Viruses

      http://virology.wisc.edu/virusworld/ Virusworld

STUDY QUESTIONS

      1 Icosahedral virus particles are NOT stabilized by:Specific “cement” or “glue” proteinsCovalent bondsInteractions between adjacent protein layersTransmembrane connections of envelope to capsid proteinsNone of the above

      2 Both picornaviruses (e.g., poliovirus) and polyomaviruses (e.g., simian virus 40) comprise small genomes packaged within icosahedral capsids.Indicate one similarity and two differences in the structures of poliovirus and simian virus 40 capsidsExplain how ONE of these capsids does not conform to the rules of quasiequivalence

      3 Which of the following statements describes interactions among components of virus particles?Subunits usually associate via covalent bondsEach subunit has different bonding contacts with its neighborsCapsid subunits cannot interact with the internal viral genomeSubunits usually associate noncovalentlySubunit-subunit interactions are always sufficient to stabilize virus particles

      4 It has long been known that virus particles can contain host cell molecules.Why is it difficult to be sure that host cell molecules found in enveloped virus particles are packaged specifically?If specific incorporation of a cellular protein into particles of a virus had been demonstrated, how would you investigate the functional importance of capture of the cellular protein?

      5 Viral envelopes:Are invariably derived from host cell membranesContain viral glycoproteins with external and internal domains connected by transmembrane segmentsCan lie above or underneath a capsidAre generally impermeable to ions and charged moleculesAll of the above

      6 What are the three modes of packing viral genomes in virus particles? Give an example of each mode of packaging.

      7 Characteristic features of large virus particles do NOT include:Distinct parts with helical or icosahedral symmetryThe presence of multiple viral enzymesStructures dedicated to exit of the viral genomeMore than a single membraneA large DNA or RNA genome

      8 Mature virus particles are said to be metastable.Explain what is meant by this term and why virus particles must be metastablePredict the consequences of a mutation that precludes formation of metastable virus particles during assembly and maturation

      9 Which of the following statements about helical symmetry is INCORRECT?Helical viruses can contain RNA or DNA genomesThese genomes can be packaged by either specialized nucleic acid binding proteins or direct contact with coat proteinsAs the structure of a helix is open, the largest known viruses display helical symmetryHelical viruses can be naked or envelopedViral enzymes are present in many helical viruses that reproduce in animal cells

      10 You have recently isolated a virus associated with a human disease. The virus particles are spherical, ~100 nm in diameter, and possess an envelope. Preliminary genome sequence analysis suggests the virus is not related to known human viruses.Indicate how you would determine the structure of this virus, and the rationale for your choice of methodWhich protein topology would you be most likely to find in the