Principles of Virology. Jane Flint

Principles of Virology - Jane Flint


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the double-stranded DNA genome (red). Adapted from Veesler D et al. 2013. Proc Natl Acad Sci U S A 110:5504–5509, with permission. Courtesy of C.-Y. Fu, The Scripps Research Institute. (B) Schematic comparison of archaeal monolayer membrane-forming and eukaryotic bilayer membrane-forming lipids.

       Khayat R, Fu CY, Ortmann AC, Young MJ, Johnson JE. 2010. The architecture and chemical stability of the archaeal Sulfolobus turreted icosahedral virus. J Virol 84:9575–9583.

       Veesler D, Ng TS, Sendamarai AK, Eilers BJ, Lawrence CM, Lok SM, Young MJ, Johnson JE, Fu CY. 2013. Atomic structure of the 75 MDa extremophile Sulfolobus turreted icosahedral virus determined by CryoEM and X-ray crystallography. Proc Natl Acad Sci U S A 110:5504–5509.

      The high-resolution viral glycoprotein structures mentioned above are those of the large external domains of the proteins that had been cleaved from the viral envelope by proteases. This treatment facilitates crystallization but, of course, precludes analysis of membrane-spanning or internal segments of the proteins, both of which may contribute to the structure or function of the proteins: membrane-spanning domains can contribute to the stability of oligomeric glycoproteins, as in influenza virus hemagglutinin (HA), while internal domains can anchor the envelope to internal structures. Improvements in resolution achieved by application of cryoelectron microscopy or tomography have allowed visualization of these segments of glycoproteins of some enveloped viruses.

       Other Envelope Proteins

      The envelopes of some viruses, including orthomyxoviruses, herpesviruses, and poxviruses, contain integral membrane proteins that lack large external domains or possess multiple membrane-spanning segments. Among the best characterized is the influenza A virus M2 protein. This small (97-amino-acid) protein is a minor component of virus particles. In the viral membrane, two disulfide-linked M2 dimers associate to form a noncovalent tetramer that functions as an ion channel. This viral ion channel is the target of the influenza virus inhibitor drug amantadine (Volume II, Fig. 9.13). The effects of this drug, as well as of mutations in the M2 coding sequence, indicate that M2 plays important roles during both entry, by controlling the pH of the virus particle interior (Chapter 5), and release of newly assembled virus particles (Chapter 13). M2 belongs to a class of channel-creating viral proteins called viroporins, which are present in a number of other enveloped viruses, such as hepatitis C virus and Sindbis virus, but also in nonenveloped viruses like simian virus 40 and papillomaviruses.

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      Enveloped viruses of several families contain an additional protein layer that mediates interactions of the genome-containing structure with the viral envelope. In the simplest case, a single viral protein, termed the matrix protein, welds an internal ribonucleoprotein to the envelope. This arrangement is found in members of several groups of (−) strand RNA viruses (Fig. 4.6C; Appendix, Fig. 17 and 31). Retrovirus particles also contain an analogous, membrane-associated matrix protein (MA), which is closely associated with the inner surface of the viral envelope.


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