Viruses are "particles" composed of nucleic acid, protein, and
(for some viruses) lipid. The surface proteins allow the virus particle to attach
to and enter into a susceptible host cell, and once inside, the nucleic acid
can somehow get replicated and expressed. Many new virus particles may get produced
and released from the (usually dying) cell. This virus life cycle, which typically
takes less than 24 hours for viruses that infect humans, may repeat over and
over as long as there are host cells available or until the host organism's
immune system successfully counters the infection. Pathology to the host can
result directly from the destruction of many millions of host cells and/or indirectly
from the overall effects of the immune response.
1. What is the simplest possible virus life cycle?
Figure 1 (below) shows a hypothetical virus with a genome
of just one gene, which codes for a protein which aggregates to form the capsid
of the virion. For a virus to be this simple, it would have to depend completely
on host cell enzymes and machinery for viral genome replication, transcription,
and translation. There is no known virus that
is this simple.
2. What are the genomes of the major viruses infecting
humans?
Table 1
(link) describes the genomes of some of the major viruses infecting humans.
A good "order of magnitude estimate" for virus genomes is that one gene takes
up about a thousand bases. Thus, we see that all of the RNA genome viruses have
about ten genes. Some of the DNA viruses also have about ten genes, while others,
particularly the herpesviruses and the poxviruses, have about a hundred genes.
3. What are the basic geometries of virions (virus particles)?
Some figures from A. J. Cann's 2001 book Principles of Molecular Virology show examples of viruses with
helical and icosahedral capsid structures.
As shown in Figure 2.3, the rhabdoviruses (such as rabies) have a helical nucleocapsid
surrounded by a lipid-protein envelope. Most of the other group V viruses also
have a virion structure consisting of a helical nucleocapsid surrounded by an
envelope. In terms of structure and the mechanism of assembly, the most highly
characterized viral helical capsid is that of Tobacco Mosaic Virus, TMV, as
shown in Figure 2.16.
Figures 2.4 and 2.5 show basic icosahedral geometry, and Figure 2.6 shows the
"triangulation number 3" icosahedral structure of picornavirus virions
(poliovirus, rhinovirus, and hepatitis A virus).
Some other viruses have an icosahedral-based structure that is significantly
more complex. In the reoviruses, there is a complicated "doubled-shelled"
icosahedral structure surrounding an inner core (Figure 2.14). In the herpesviruses,
there is an icosahedral capsid surrounded by an amorphous layer called the "tegument"
and a lipid-bilayer envelope (membrane) that contains numerous glycoproteins.
The largest and most complex virions are those of the poxviruses, as shown in
Figure 2.11. Poxvirus virions contain two lipid bilayer envelopes, and an overall shape that is distinctly different from other viruses.
4. What do some of these more complicated virus structures look like when analyzed by the most recent electron microscopy techniques?
A new technique called cryo-electron tomography has been applied to the study of several complicated enveloped viruses within the past few years. The links below take you to the abstracts of four articles. Go to the full length articles and look at the figures in some detail prior to class. In addition, look for links to more recent journal articles that have cited these papers.
Herpes Simplex Virus: Grunewald et al. Science, 2003
Poxvirus (Vaccinia): Cyrklaff et al., Proc. Nat. Acad. Sci., 2005
Influenza Virus: Harris et al., Proc. Nat. Acad. Sci., 2006
Human Immunodeficiency Virus: Zhu et al., Nature, 2006
Summary:
One can imagine the simplest possible virus and its life cycle; but no known
virus is this simple. Of the viruses that infect us and other animals, there
is a wide variety of structural and genome variation. Virions have capsid proteins
packed in either helical or icosahedral symmetry, and about half have a lipid-protein
envelope. Viral genomes are either DNA or RNA, single stranded or double stranded.
DNA viruses have genome sizes of anywhere from several thousand bases to about
two hundred thousand bases, while RNA viruses have genomes that fall into a
much narrower range, from about 8 to 20 thousand bases.
Figure 1