| Cells Infected | Virus |
|---|---|
| B lymphocytes | Epstein–Barr virus (herpesvirus) |
| Some retroviruses | |
| T lymphocytes | Human T‐cell leukemia virus |
| HIV | |
| Human herpesvirus 6 | |
| Human herpesvirus 7 | |
| Monocytes | Measles virus |
| Varicella‐zoster virus (herpesvirus) | |
| HIV | |
| Parainfluenza virus | |
| Influenza virus | |
| Rubella (German measles) virus | |
| Cytomegalovirus (herpesvirus) |
Multiplication of virus to high levels – occurrence of disease symptoms
Viral replication at specific target tissues often defines symptoms of the disease. The nature of the target and the host response are of primary importance in establishing symptoms. The ability of a virus to replicate in a specific target tissue results from specific interactions between viral and cellular proteins. In other words, one or another viral protein can recognize specific molecular features that define those cells or tissues favored for virus replication. These virus‐encoded proteins, thus, have a major role in specifying the virus's tissue tropism. Host factors, such as speed of immune response and inflammation, also play a major role. For example, a head cold results from infection and inflammation of the nasopharynx. Alternatively, liver malfunction due to inflammatory disease (hepatitis) could result from a viral infection in this critical organ.
One major factor in viral tropism is the distribution and occurrence of specific viral receptors on cells in the target tissue. The role of such receptors in the infection process is described in Part II, Chapter 6. For the purposes of the present discussion, it is enough to understand that there must be a specific and spatially close interaction between proteins at the surface of the virus and the surface of the cell's plasma membrane for the virus to be able to begin the infection process.
One example of the role of receptors in tissue tropism involves the poliovirus receptor, which is found on cells of the intestinal mucosa and in lymphatic tissue. A related molecule is also present on the surface of motor neurons, which means that neurotropic strains of poliovirus can invade, replicate in, and destroy these cells under certain conditions of infection. In another example, HIV readily infects T lymphocytes by recognizing the CD4 surface protein in association with a specific chemokine receptor that serves as a coreceptor. Rabies virus's ability to remain associated with nervous tissue probably is related to its use of the acetylcholine receptor present at nerve cell synapses. The ability of vaccinia virus (like the related smallpox virus) to replicate in epidermal cells is the result of its use of the epidermal growth factor receptor on such cells as its own receptor for attachment.
While tissue tropism is often understandable in terms of a specific viral receptor being present on the surface of susceptible cells, the story can be quite complicated in practice. This is the case for Epstein–Barr virus(EBV), which is found in B lymphocytes in patients who have been infected with the virus. It is thought that primary infection of epithelial cells in the mucosa of the nasopharynx, followed by association with lymphocytes during development of the immune response, leads to infection of B cells that carry the EBV‐specific receptor, CD21.
Even though the infection of target tissue is usually associated with the occurrence of symptoms of that viral infection, the target is not always connected with the spread of a virus subsequent to infection. For example, HIV infection can be readily spread from an infected individual long before any clinical symptoms of the disease (AIDS) are apparent. An individual can undergo a subclinical reactivation episode where there is virus in the saliva, but no fever blister can transmit HSV. Finally, paralytic polio is the result of a “dead‐end” infection of motor neurons, and the resulting death of those neurons and paralysis have nothing to do with spread of the virus.
Later stages of infection – changes in the cell
Eventually, viral infection leads to distinct changes within the infected cell. Such alterations are termed cytopathology. These effects can most easily be observed in viral infected cells in culture. Viral‐induced changes might be found in both the cytoplasm and the nucleus, depending, of course, on the virus in question. Table 2.2 lists some examples of such cytopathic outcomes of infection.
The later stages of infection – the immune response
Infections with virus do not necessarily lead to any or all symptoms of a disease. The severity of such symptoms is a function of the virus genotype, the amount of virus delivered to the host, and the host's general immune competence – the factors involved with virulence of the infection. The same virus in one individual can lead to an infection with such mild symptoms of disease that they are not recognized for what they are, while infection of another individual can lead to severe symptoms.
Generally, a virus infection results in an effective and lasting immune response. This is described in more detail in Part II, Chapter 7; briefly, the host's immune response (already activated by the presence of viral antigens at any and all sites where virus is replicating) reaches its highest level as clinical signs of the disease manifest.
A full immune response to virus infection requires the maturation of B and T lymphocytes. The maturation of lymphocytes results in the production of short‐lived effector T cells, which kill cells expressing foreign antigens on their surfaces. Another class of effector T cells helps in the maturation of effector B cells for the secretion of antiviral antibodies. Such a process takes several days to a week after stimulation with significant levels of viral antigen. An important part of this immune response is the generation of long‐lived memory lymphocytes to protect against future re‐infection.
In addition to the host's immune response, which takes some time to develop, a number of nonspecific host responses to infection aid in limitation of the infection and contribute to virus clearing. Interferons quickly render sensitive cells resistant to virus infection. Therefore, their action limits or interferes with the ability of the virus to generate high yields of infectious material. Other responses include tissue inflammation, macrophage destruction of infected cells, and increases in body temperature, which can result in suboptimal conditions for virus infection.
Table 2.2 Some examples of viral cytopathic effect.
| Cytopathic Effect | Features | Virus |
|---|---|---|
| Lysis | Lytic infection ultimately results in the loss of integrity of the plasma membrane of the cell. | Enteroviruses |