With rabies, for example, injection of virus via the saliva of an animal bearing active disease leads to unapparent early infection, followed by a long incubation period of two to eight weeks or more depending on the species and individual. During this time, the infected animal is a walking “time bomb.” The symptoms of disease (irritability, frenzy, and salivation) are all important parts of the way the virus is spread among individuals. The very long incubation period allows animals bearing the disease to carry on normal activities, even breed, before the symptoms almost inevitably presaging death appear. A hypothetical viral infection that might lead to these physiological and behavioral changes but that resulted in a quick death could not be spread in such a way.
HIV/AIDS
AIDS, which is characterized by an acute infection by HIV and a latent period in which HIV can be transmitted, followed by severe disease, is an example of a “new” zoonotic viral disease. In humans, virus spread is often the result of behavioral patterns of infected individuals during HIV's long latent period. This pattern of spread makes it unlikely that there is any selective pressure over time toward amelioration of the late severe symptoms of AIDS.
Prion diseases
We have noted in Chapter 1 that while prions are not viruses, many of the principles developed for the study of viral diseases can be applied to study of the pathology of prion‐associated diseases. The prion‐caused encephalopathies are, perhaps, the extreme example of an infectious disease with a long incubation period. Periods ranging from 10 to 30 years between the time of exposure and onset of symptoms have been documented. Prion‐induced encephalopathy does not lead to any detectable immune response or inflammation, probably because the prion is a host protein and the CNS is isolated from normal immune surveillance. The course of the disease is marked by a slow, progressive deterioration of brain tissue. Only when this deterioration is significant enough to lead to behavioral changes can the disease be discerned and diagnosed. No treatment or vaccination strategy is available at this time for human prion diseases, but a partly successful vaccine to prevent prion‐mediated chronic wasting disease of cervids (deer and elk) has been developed.
SOME VIRAL INFECTIONS TARGETING SPECIFIC ORGAN SYSTEMS
While all the organ systems of the vertebrate host have important or vital functions in the organism's life, several play such critical roles that their disruption leads to serious consequences or death. Among these are the CNS with its influence on all aspects of behavior both innate and learned, the circulatory system, the immune system, and the liver. Virus infections of these systems are often life‐threatening to the infected individual, and the tissue damage resulting from infection can lead to permanent illness or death. For example, destruction of CD4+ T cells of the immune system by HIV is the major symptom of AIDS and leads in >90% of untreated cases to death from opportunistic infections and neoplasms. Other viruses can cause as devastating a disease as HIV, but most viral infections are not as often fatal. A consideration of some CNS and liver virus infections provides some interesting examples of both destructive and limited disease courses.
The different patterns of sequelae following infection of a common target organ are also important demonstrations of several features of virus infection and pathogenesis.
First, specific tissue or cell tropism is a result of highly specific interactions between a given virus and the cell type it infects. Depending on the type of cell infected, the severity of symptoms, and the nature of the damage caused by the infection, different outcomes of infection are evident.
Second, persistent infection is a complex process. It is, in part, the result of virus interacting with and modulating the host's immune system. Often, persistence involves the virus adapting to a continuing association with the target cell itself.
Third, classifying viruses by the diseases they cause is not a particularly useful exercise when trying to understand relationships among viruses.
Fourth, and finally, viruses spread by very different routes can target the same organ. The movement of virus within the host is as important as the initial port of entry for the virus.
Viral infections of nerve tissue
The vertebrate nerve net can be readily divided into peripheral and central portions. The peripheral portion functions to move impulses to and from the brain through connecting circuits in the spinal cord. Viral infections of nerve tissue can be divided into infections of specific groups of neurons: neurons of the spinal cord (myelitis), the covering of the brain (meningitis), and neurons of the brain and brain stem itself (encephalitis).
The brain and CNS have a privileged position in the body and are protected by a physical and physiological barrier from the rest of the body and potentially harmful circulating pathogens. This barrier, often referred to as the blood–brain barrier, serves as an effective but incomplete barrier to pathogens. Viruses that migrate through neurons can breach it and traverse synapses between peripheral and central neurons, by physical destruction of tissue due to an active infection, by direct invasion via olfactory neurons (which are not isolated from the CNS), or by other less well‐characterized mechanisms. Certainly, invasion of the CNS by pathogens is not all that rare since a specific set of cells in the CNS, the microglial cells, function in manners analogous or identical to macrophages in other tissues.
Many viruses can infect nerve tissue, and while some such infections are dead ends, other viruses specifically target nerve tissue. Viruses that do infect nerve tissue tend to favor one or another portion, and whereas the discrimination is not complete, many viruses, such as enteroviruses and genital HSV (HSV‐2), tend to be causative agents of meningitis; while others, such as rabies and facial HSV (HSV‐1), are almost always associated with encephalitis. Viral or aseptic meningitis tends in general to be less life‐threatening than the majority of viral infections associated with encephalitis, but all are serious and can lead to debilitating diseases.
While many viral infections of the brain can have grave consequences, such consequences are not always the case. Some viral infections of the CNS have reasonably benign prognoses if proper symptomatic care is provided to the afflicted individual. Viruses that target the brain can be broken into several operational groupings, depending on the nature of brain involvement and whether it and associated tissue are a primary or secondary (“accidental”) target.
Examples of viral encephalitis with grave prognosis
Rabies
Once the symptoms of disease become apparent, rabies virus infections are almost always fatal. The virus targets salivary tissue in the head and neck in order to provide itself with an efficient medium for transmission to other animals. Involvement of the CNS and brain is eventually widespread, with ensuing neuronal dysfunction. Prior to this, however, the involvement is only with specific cells that lead to alterations in the afflicted animal's behavior and ability to deal with sensory stimuli. During this period, which is often preceded by a prodromal period of altered behavioral patterns, the animal can be induced to an aggressive biting frenzy by loud sounds or by the appearance of other animals. This course is the “furious form” of the disease. This behavioral change is most marked for carnivores such as dogs, cats, and raccoons, but can be observed in other infected animals such as squirrels and porcupines. The behavioral changes obviously have a marked impact
