which contains the double-stranded DNA genome of some 0.6 Mbp, is enclosed within what is thought to be a lipid membrane, in turn encased in a thick protein layer (the tegument). The apex of pithovirus is closed by a protruding “cork” with a hexagonal, grid-like appearance (Fig. 4.29C and D). Following uptake of virus particles into host cells by phagocytosis, this unusual cork structure is expelled to allow fusion of the viral nucleoid membrane with that of the cellular vacuole. Unprecedented assemblies specialized for release of the viral genome in host cells may prove to be a characteristic property of the very large viruses.
Figure 4.29 Virus particles with alternative architectures. Structural features of the poxvirus vaccinia virus. (A) Surface rendering of intracellular mature particles of vaccinia virus reconstructed from cryo-electron tomograms showing the brick shape and irregular protrusions from the surface. (B) Translucent visualization of the reconstructed particle volume showing the dumbbell-shaped core and external membrane. A and B reprinted from Cyrklaff M et al. 2005. Proc Natl Acad Sci U S A 102:2772–2777, with permission. Courtesy of J.L. Carrascosa, Universida Autonoma de Madrid. The virus Pithovirus sibericum was isolated following culture of a suspension of soil from a sample of permafrost collected in 2000 in Siberia. (C) Morphology of this virus particle, viewed by energy-filtered cryo-EM to facilitate visualization of thick, ice-embedded particles. The internal nucleoid, which appears rather featureless, is likely covered by a membrane, a thick protein layer termed the tegument, and a low-density outer layer. (D) The apical cork, which is made up of vertical fibers and hence appears striated, resides at one end of the particle. C and D reprinted from Okamoto K et al. 2017. Sci Rep 7:13291, under license CC BY 4.0. Courtesy of K. Okamoto, Uppsala University, Sweden.
Other Components of Virions
Some virus particles comprise only the nucleic acid genome and structural proteins necessary for protection and delivery into a host cell. However, many contain additional viral proteins, which are generally present at much lower concentrations but essential or important for establishing an efficient infectious cycle (Table 4.3).
Enzymes
Many types of virus particles contain enzymes necessary for synthesis of viral nucleic acids. These enzymes generally catalyze reactions unique to virus-infected cells, such as synthesis of viral mRNAs from an RNA template or of viral DNA from an RNA template (retroviral reverse transcriptases). However, virions of vaccinia virus contain a DNA-dependent RNA polymerase, analogous to cellular RNA polymerases, as well as several enzymes that modify viral RNA transcripts (Table 4.3). This complement of enzymes is necessary because transcription of the viral double-stranded DNA genome takes place in the cytoplasm of infected cells, whereas cellular DNA-dependent RNA polymerases and the RNA-processing machinery are restricted to the nucleus. Other types of enzymes found in virus particles include integrase, cap-dependent endonuclease, and proteases. The proteases sever covalent connections within polyproteins or precursor proteins from which some virus particles assemble, a reaction that is necessary for the production of infectious particles (Chapter 13).
Other Viral Proteins
Virus particles may also contain additional viral proteins that are not enzymes but nonetheless are important for an efficient infectious cycle. Among the best characterized are the protein primers for viral genome replication that are covalently linked to the genomes of picornaviruses such as poliovirus and adenoviruses. Others include several tegument proteins of herpesviruses, such as the VP16 protein, which activates transcription of viral immediate-early genes to initiate the viral program of gene expression. The cores of vaccinia virus also contain proteins that are essential for transcription of viral genes, as they allow recognition of viral early promoters. Other herpesvirus tegument proteins induce the degradation of cellular mRNA or block cellular mechanisms by which viral proteins are presented to the host’s immune system. Retroviruses with complex genomes, such as human immunodeficiency virus type 1, contain additional proteins required for efficient viral reproduction in certain cell types. These proteins are discussed in Volume II, Chapter 12.
Table 4.3 Some virion enzymes
| Virus | Protein | Function(s) |
|---|---|---|
| Adenovirus | ||
| Human adenovirus type 2 | L3 23k | Protease; production of infectious particles |
| Herpesvirus | ||
| Herpes simplex virus type 1 | VP24 | Protease; capsid maturation for genome encapsidation |
| UL13 | Protein kinase | |
| Vhs | RNase | |
| Orthomyxovirus | ||
| Influenza A virus | P proteins | RNA-dependent RNA polymerase; synthesis of viral mRNA and vRNA; cap-dependent endonuclease |
| Poxvirus | ||
| Vaccinia virusa | DNA-dependent RNA polymerase (8 subunits) | Synthesis of viral mRNA |
| Poly(A) polymerase (2 subunits) | Synthesis of poly(A) on viral mRNA | |
| Capping enzyme (2 subunits) | Addition of 5' caps to viral pre-mRNA | |
| DNA topoisomer ase | Sequence-specific nicking of viral DNA | |
| Proteases 1 and 2 | Virus particle morphogenesis | |
| Reovirus | ||
| Reovirus type 1 | λ2 | Guanylyltransferase |
| λ3 | Double-stranded RNA-dependent RNA polymerase | |
|
Retrovirus
| ||
