In animal cells, the process of transformation often results in altered growth properties of the cell and can result in the generation of cells that have some or many properties of cancer cells. There are instances, however, where the coexistence of a cell and an infecting virus leads to few or no detectable changes in the cell. For example, herpes simplex virus(HSV) can establish a latent infection in terminally differentiated sensory neurons. In such cells there is absolutely no evidence for expression of any viral protein at all. Periods of viral latency are interspersed with periods of reactivation (recrudescence) where virus replication is reestablished from the latently infected tissue for varying periods of time.
Some viral infections of plant cells also result in stable association between virus and cell. Indeed, the variegation of tulip colors, which led to economic booms in Holland during the sixteenth century, is the result of such associations. Many other examples of mosaicism resulting from persisting virus infections of floral or leaf tissue have been observed in plants. However, many specific details of the association are not as well characterized in plants as in animal and bacterial cells.
Stages of virus replication in the cell
Various patterns of replication as applied to specific viruses, as well as the effect of viral infections on the host cell and organism, are the subject of many of the following chapters in this book. The best way to begin to understand patterns of virus replication is to consider a simple general case: the productive infection cycle – this is shown schematically in Figure 2.2. A number of critical events are involved in this cycle. The basic pattern of replication is as follows:
1 The virus specifically interacts with the host cell surface, and the viral genome is introduced into the cell. This involves specific recognition between virus surface proteins and specific proteins on the cell surface (receptors) in animal and bacterial virus infections.
2 Viral genes are expressed using host cell processes. This viral gene expression results in synthesis of a few or many viral proteins involved in the replication process.
3 Viral proteins modify the host cell and allow the viral genome to replicate using host and viral enzymes. While this is a simple statement, the actual mechanisms by which viral enzymes and proteins can subvert a cell are manifold and complex. This is often the stage at which the cell is irreversibly modified and eventually killed. Much modern research in the molecular biology of virus replication is directed toward understanding these mechanisms.
4 New viral coat proteins assemble into capsids, and viral genomes are included. The process of assembly of new virions is relatively well understood for many viruses. The successful description of the process has resulted in a profound linkage of knowledge about the principles of macromolecular structures, the biochemistry of protein–protein and protein–nucleic acid interactions, and the thermodynamics of large macromolecule structures.Figure 2.2 The virus replication cycle. Most generally, virus replication can be broken into the stages shown: (a) initial recognition between virus and cell and introduction of viral genetic material into the host cell, (b) virus gene expression and induction of virus‐induced modification of host, allowing (c) virus genome replication. Following this, (d) virus‐associated proteins are expressed, and (e) new virus is assembled and released, often resulting in cell death.
5 Virus is released where it can infect new cells and repeat the process. This is the basis of virus spread, whether from cell to cell or from individual to individual. Understanding the process of virus release requires knowledge of the biochemical interactions between cellular organelles and viral structures. Understanding the process of virus spread between members of a population requires knowledge of the principles of epidemiology and public health.
PATHOGENESIS OF VIRAL INFECTION
Most cells and organisms do not passively submit to virus infection. As noted in Chapter 1, the response of organisms to virus infection is a major feature of evolutionary change in its most general sense. As briefly noted, a complete understanding of pathogenesis requires knowledge of the sum total of genetic features a virus encodes that allows its efficient spread between individual hosts and within the general population of hosts. Thus, the term pathogenesis can be legitimately applied to virus infections of multicellular, unicellular, and bacterial hosts.
A major challenge for viruses infecting bacteria and other unicellular organisms is finding enough cells to replicate in without isolating themselves from other populations of similar cells. In other words, they must be able to “follow” the cells to places where the cells can flourish. If susceptible cells can isolate themselves from a pathogen, it is in their best interest to do so. Conversely, the virus, even when constrained to confine all its dynamic features of existence to the replication process per se, must successfully counter this challenge or it cannot survive.
In some cases, cells can mount a defense against virus infection. Most animal cells react to infection with many viruses by inducing a family of cellular proteins termed interferons that can interact with neighboring cells and induce those cells to become wholly or partially resistant to virus infection. Similarly, some viral infections of bacterial cells can result in a bacterial restriction response that limits viral replication. Of course, if the response is completely effective, the virus cannot replicate. In this situation, one cannot study the infection, and in the extreme situation, the virus would not survive.
Viruses that infect multicellular organisms face problems attendant with their need to be introduced into an animal to generate a physiological response fostering the virus's ability to spread to another organism (i.e., they must exhibit virulence). This process can follow different routes.
Disease is a common result of the infection, but many (if not most) viral infections result in no measurable disease symptoms – indeed, inapparent infections are often hallmarks of highly coevolved virus–host interactions. But inapparent or asymptomatic infections can be seen in the interaction between normally virulent viruses and a susceptible host as a result of many factors. A partial list includes the host's genetic makeup, host health, the degree of immunity to the pathogen in the host, and the random (stochastic) nature of the infective process.
Stages of virus‐induced pathology
Pathogenesis can be divided into stages – from initial infection of the host to its eventual full or partial recovery, or its virus‐induced death. A more‐or‐less typical course of infection in a vertebrate host is schematically diagrammed in Figure 2.3. Although individual cases differ, depending on the nature of the viral pathogen and the immune capacity of the host, a general pattern of infection would be as follows:
Initial infection leads to virus replication at the site of entry, and multiplication and spread into favored tissues. The time between the initial infection and the observation of clinical symptoms of disease defines the incubation period, which can be of variable length, depending on many factors.Figure 2.3 The pathogenesis of virus infection. Typically, infection is followed by an incubation period of variable length in which virus multiplies at the site of initial infection. Local and innate immunity, including the interferon response, counter infection from the earliest stages; and if