Basic Virology. Martinez J. Hewlett

required for the replication of the genome are encoded in that genome. There are genetic variants of viruses that have lost information either for one or more coat proteins or for replication of the genome. Such virus‐derived entities are clearly related to a parental form with complete genetic information, and thus, the mutant forms are often termed defective virus particles.

      Defective viruses require the coinfection of a helper virus for their replication; thus, they are parasitic on viruses. A prime example is hepatitis delta virus, which is completely dependent on coinfection with hepatitis B virus for its transmission.

      The hepatitis delta virus has some properties in common with a group of RNA pathogens that infect plants and can replicate in them by still‐unknown mechanisms. Such RNA molecules, called viroids, do not encode any protein, but can be transmitted between plants by mechanical means and can be pathogens of great economic impact.

      Some pathogens appear to be entirely composed of protein. These entities, called prions, appear to be cellular proteins with an unusual folding pattern. When they interact with normally folded proteins of the same sort in neural tissue, they appear to be able to induce abnormal refolding of the normal protein. This abnormally folded protein interferes with neuronal cell function and leads to disease. While much research needs to be done on prions, it is clear that they can be transmitted with some degree of efficiency among hosts, and they are extremely difficult to inactivate. Prion diseases of sheep and cattle (scrapie and “mad cow” disease) recently had major economic impacts on British agriculture, and several prion diseases (kuru and Creutzfeldt–Jacob disease[CJD]) affect humans. Disturbingly, the inadvertent passage of sheep scrapie through cattle in England has apparently led to the generation of a new form of human disease similar to, but distinct from, CJD. Details of this are covered in Part IV, Chapter 15.

      The existence of such pathogens provides further circumstantial evidence for the idea that viruses are ultimately derived from cells. It also provides support for the possibility that viruses had multiple origins in evolutionary time.

QUESTIONS FOR CHAPTER 1

      1 Viruses are a part of the biosphere. However, there is active debate concerning whether they should be treated as living or nonliving.Briefly describe one feature of viruses that is also found in cell‐based life forms.Briefly describe one feature of viruses that distinguishes them from cell‐based life forms.

      2 Why is it likely that viruses have not evolved from free‐living organisms?

      3 Give examples of infectious agents that are smaller self‐replicating systems than viruses.

      4 Ebola virus is a deadly (90% case‐fatality rate for some strains) infectious agent. Most viruses, however, are not nearly as lethal. Given the nature of viruses, why would you expect this to be so?

      5 Given that viruses are a part of the biosphere in which other organisms exist, what might be the kinds of selective pressure that viruses exert on evolution?

      6 Viruses were originally discovered because of their size, relative to known bacterial cells. Tobacco mosaic virus was called a “filterable infectious agent” by this criterion. Why is size not a good defining feature for viruses? What is a better definition?

CHAPTER 2 An Outline of Virus Replication and Viral Pathogenesis

        VIRUS REPLICATION

        Stages of virus replication in the cell

        PATHOGENESIS OF VIRAL INFECTION

        Stages of virus‐induced pathology Initial stages of infection – entry of the virus into the host The incubation period and spread of virus through the host Multiplication of virus to high levels – occurrence of disease symptoms The later stages of infection – the immune response The later stages of infection – virus spread to the next individual The later stages of infection – fate of the host

        QUESTIONS FOR CHAPTER 2

VIRUS REPLICATION

      Viruses must replicate in living cells. The most basic molecular requirement for virus replication is for a virus to induce either profound or subtle changes in the cell so that viral genes in the genome are replicated and viral proteins are expressed. This will result in the formation of new viruses – usually many more than the number of viruses infecting the cell in the first place. When reproducing, viruses use at least part of the cell's equipment for replication of viral nucleic acids and expression of viral genes. They also use the cell's protein synthetic machinery, and the cell's metabolic energy resources.

The dimensions and organization of “typical” animal, plant, and bacterial cells are shown in Figure 2.1. The size of a typical virus falls in the range between the diameters of a ribosome and of a centriolar filament. With most viruses, infection of a cell with a single virus particle will result in the synthesis of more than one (often by a factor of several powers of 10) infectious virus. Any infection that results in the production of more infectious virus at the end than at the start is classified as a productive infection. The actual number of infectious viruses produced in an infected cell is called the burst size, and this number can range from less than 10 to over 10 000, depending on the type of cell infected, the nature of the virus, and many other factors.

Figure 2.1 Dimensions and features of “typical” (a) animal, (b) plant, and (c) bacterial cells. The dimensions of plant and animal cells can vary widely, but an average diameter of around 50 μm (5 × 10⁻⁵ m) is a fair estimate. Bacterial cells also show great variation in size and shape, but the one shown here is Escherichia coli, the true “workhorse” of molecular biologists. Its length is approximately 5 μm. Based on these dimensions and shapes of the cells shown, the bacterial cell is approximately 1/500th of the volume of the eukaryotic cell shown. Virus particles also vary greatly in size and shape, but generally range from 25 to 200 nm (0.25–2.00 × 10⁻⁷ m).

      Infections with many viruses completely convert the cell into a factory for replication of new viruses. Under certain circumstances and/or in particular cells, however, virus infection leads to a state of coexistence between the cell and infecting virus, which can persist for as long as the life of the host. This process can be a dynamic one in which there is a small amount of virus produced constantly, or it can be passive where the viral genome is carried as a “passenger” in the cell with little or no evidence of viral gene expression.