This lecture will define and discuss the basic principles of viral pathogenesis, the entire process by which viruses cause disease. Viral disease is a sum of the effects on the host of virus replication and of the immune response.
Interest in viral pathogenesis stems from the desire to treat or eliminate viral diseases that affect humans. This goal is achieved in part by identifying the viral and host genes that influence the production of disease. Progress in understanding the molecular basis of viral pathogenesis comes largely from studies of animal models. The mouse has become a particularly fruitful host for studying viral pathogenesis because the genome of this animal can be manipulated readily. In some cases, non-human hosts can be infected with the same viruses that infect humans, but close relatives of human viruses must often be used.
Three requirements must be satisfied to ensure successful infection in an individual host:
Sufficient virus must be available to initiate infection
Cells at the site of infection must be accessible, susceptible, and permissive for the virus
Local host anti-viral defense systems must be absent or initially ineffective.
To infect its host, a virus must first enter cells at a body surface. Common sites of entry include the mucosal linings of the respiratory, alimentary, and urogenital tracts, the outer surface of the eye (conjunctival membranes or cornea), and the skin (Fig. 1).
Figure 1. Sites of viral entry into the host.
The most common route of viral entry is through the respiratory tract. The combined absorptive area of the human lung is almost 140 m2. Humans have a resting ventilation rate of 6 liters of air per minute, which introduces large numbers of foreign particles and aerosolized droplets into the lungs with every breath. Many of these particles and droplets contain viruses. Fortunately, there are numerous host defense mechanisms to block respiratory tract infection. Mechanical barriers play a significant role in anti-viral defense. For example, the tract is lined with a mucociliary blanket consisting of ciliated cells, mucous-secreting goblet cells, and sub-epithelial mucous-secreting glands (Fig. 2). Foreign particles deposited in the nasal cavity or upper respiratory tract are trapped in mucus, carried to the back of the throat, and swallowed. In the lower respiratory tract, particles trapped in mucus are brought up from the lungs to the throat by ciliary action. The lowest portions of the tract, the alveoli, lack cilia or mucus, but macrophages lining the alveoli ingest and destroy particles. Other cellular and humoral immune responses also intervene.