A Brief Introduction to Virology Part I
Viruses are, by far, among the most difficult organisms on the planet to deal with. They are not truly living things. They do not carry out their own metabolism, nor do they reproduce on their own. They require a host to perform the activities we associate with living organisms.
Two of the best definitions of viruses I’ve ever heard were these: “Viruses are bad news wrapped in a protein coat”, and “Viruses are the ultimate parasites.” Although scientifically simplistic, these definitions capture the essence of what viruses really are. I must admit here, though they are my favorite definitions, I can not recall from whom I heard them. Suffice it for me to say publicly that they are not mine.
Despite their distinct classification, be they picornaviruses, paramyxoviruses, filoviruses, orthomyxoviruses, flavoviruses, or any other members of the virus families, they all follow pretty much the same pattern in dealing with a host: Attachment, Penetration, Uncoating, Replication, Assembly and Exit. Although they can use different methods in achieving the above sequence, the end result is the same, the propagation of new, viable virions, or viral particles. Their only goal is to reproduce.
In this article, I’m going to take a brief look at the science of Virology, starting out with an overview of virus morphology or structure, and a glimpse at “Attachment, Penetration and Uncoating. It is my hope to generate a short series of these articles, next of which will look at Replication, Assembly and Exit.
It must be kept in mind that this is only an overview, and is not intended to serve as a full text or description of the subject.
Viruses come in all shapes and sizes. For example, within the animal viruses sizes range from 18 to 26 nanometers (nm), for the parvoviruses, to 130to 280nm for the poxviruses. They can be round, linear, oblong, brick-shaped or, as in the case of bacteriophages, shaped somewhat like the lunar lander. What they all have in common is an outer protein coat called a capsid or nucleocapsid if the genetic material is attached.
The protein coat can come in the form of layers of proteins laid together around the genetic material like a slinky, or it can create a series of triangles that come together to form a geodesic dome-like structure around the viral genome.
Viruses are classified as either naked or enveloped, depending on whether or not they have an outer layer of phospholipids generally derived from the host cell. There are also complex viruses, such as the poxvirus, which carries some of the requisite enzymes and other replication factors, so that they do not have to rely on the host cell for these. As a consequence, they are the only double-stranded DNA viruses able to replicate inside the cytoplasm of their host cell without ever entering the nucleus.
Viral Genetics and Classification
To begin, the first thing that must be mentioned is that viral genomes can consist of either DNA or RNA, but not both. Some viruses, like the retroviruses, can contain multiple copies of a genome, but not two different types. Each of these uses a different strategy to achieve their final goal: replication. These genomes can be linear, double-stranded, circular, or segmented, as in the case of the orthomyxoviruses (flu viruses).
Early classification of viruses was done following the Linnaean system. This classification scheme was proposed in 1962 by Lwoff, Horne and Tournier. It was centered on four properties of viruses: a.) Type of nucleic acid, DNA or RNA, b.) Capsid shape or symmetry, c.) Viral capsid enveloped or naked, and d.) Size and shape of the capsid.
Later, the International Committee on Taxonomy of Viruses adopted some but not all of the aforementioned classification scheme. David Baltimore proposed a system that was based on Crick’s (of Watson and Crick fame) central dogma theory. This theory states that all encoded information within cellular DNA is expressed as mRNA (messenger RNA), which in turn is translated into proteins. What Baltimore proposed was to classify viruses according to the pathways they used to go from genome to mRNA.
To understand Baltimore’s system you must understand the terminology. His system is based on whether or not the mRNA is positive stranded or negative stranded. In a nutshell, positive stranded mRNA can be directly translated into proteins. Negative stranded mRNA is a compliment of positive strand mRNA and must first be converted into a functional positive strand mRNA.
There are six classifications under the Baltimore system:
Class I Double-stranded DNA.
Class II Single-stranded DNA.
Class III Double-stranded RNA (here, one of the strands is positive sense.)
Class IV Single-stranded RNA, in which the mRNA is a positive strand.
Class V Single-stranded RNA, in which the mRNA is a negative strand.
Class VI Positive-stranded RNA, but here replication requires synthesis of double-stranded DNA first. These are the retroviruses (RNA-tumor viruses).
There are also some subclasses, IIa, IIb, IVa and IVb, but we need not concern ourselves with these at this point.
Attachment, Penetration and Uncoating
For a virus to be successful in producing more of itself, it must first be able to invade a host. To do this, as was mentioned earlier, it must attach to the cell, penetrate to the interior of the cell and have the ability to shed its protective protein coat. Additionally, the host cell to which the virus attaches must be both susceptible and permissive. That is, it must not only be capable of allowing the virus to enter, but also be able to support the activities needed by the virus to produce progeny. A virus’s predilection for a particular type of cell is called Tropism. An example is the Tropic affinity that the HIV virus has for human helper T cells, macrophages or other antigen-presenting cells (APCs).
In short, viruses and cell surfaces interact though attachment and receptor proteins on the virus and cell respectively. Some of these interactions are mediated by strong affinities between the viral attachment proteins and the cellular receptors. Some have weaker affinities, and some require multiple bindings, that is, binding the main attachment protein to its primary receptor and a co-receptor. The viral host range is determined by the variety of cellular receptors a specific virus has the ability to utilize. The lower the number of host cell receptors a virus can use the narrower the host range.
Another method used by enveloped viruses is that of the fusion protein. This protein allows the membranes of the cell and virus to fuse together. As most enveloped viruses derive their envelope from the cell’s plasma membrane (some use the endoreticular membrane), the phospholipids from both virus and cell can merge together. It is believed that the fusion process is pH-dependant. In effect, the merging of viral and cellular envelopes is governed by hydrophobic interactions of the two membranes.
For the enveloped viruses, this is both attachment and penetration. For the naked viruses, penetration following attachment is usually governed by endocytosis, called viropexis. The cell is activated to bring the virus inside.
Once inside the cell, the virus must shed its protein coat. In many cases, this is a pH-dependant mechanism regulated by lysozymes. In other cases, a virion (virus particle) will bind to a clathrin-coated pit. Acidification induces a conformational change in the viral capsid structure. In some cases, as with the picornaviruses it becomes a kind of cascade. The acidification process releases one of the viral proteins, leaving hydrophobic regions of a remaining protein exposed. These regions then induce the release of the viral genome into the cytoplasm.
Having achieved attachment, penetration and uncoating, the virus is now free to go about its primary mission making more of itself.