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Viruses can only survive by entering and parasitizing the cells of a host. Because viruses cannot live independently of their interaction with the parasitized host cell, all viruses have evolved strategies for coexisting with cells, while these cells continue to carry out physiologic functions as part of specific tissues or organs. It is the complex interplay between viral and host properties that determines the relationship that the virus will experience with its host in vivo, whether resulting in disease or not. The interplay between viral and host features thus determines the pathogenesis of infection.

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Pathogenesis has generally been conceptualized as the series of sequential steps starting with entry of the virus into host cells, and progressing through survival of the virus and dissemination of the virus in the host, to shedding of the virus from the host to spread to new individuals where the virus continues its life cycle. In the animal host, every virus must overcome a series of defenses in order to enter, disseminate, and localize in the ideal target tissue; replicate; and shed to infect new hosts. At each stage, the host possesses specific mechanisms to inhibit the survival of the virus, and the virus has evolved ways to counteract these mechanisms. Some of these strategies for evading host defenses are common to different viruses. Considering viral pathogenesis in this way as the stepwise unfolding of events within the host is useful and simple because thus far we know far more in most cases about the virus itself than we do about the host side of the complex interplay. When applying this model of viral pathogenesis, however, often the steps may not occur sequentially, but rather several steps may be occurring at the same time, or several alternate pathways may be taken simultaneously.

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As new understanding of the host contributions to viral pathogenesis emerges, the impact that an individual's genetic makeup has on susceptibility to infectious disease has become clear. In fact, recent data suggest that an error in a single gene is enough to dramatically alter an individual's susceptibility to viral infections.1 It is becoming apparent that pathogenesis should likely, in the future, be conceptualized as a balance between the viral agent and the host’s immunologic and genetic makeup.

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Genetic Susceptibility to Infection

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For respiratory syncytial virus (RSV), several abnormal underlying conditions that predispose to severe forms of disease have been enumerated, and include prematurity, preexisting lung disease, and various forms of immunodeficiency. However, it is not yet known why some apparently normal infants and children proceed from initial infection to severe lower respiratory tract disease, whereas others experience a relatively mild, self-limited illness. Recent evidence now points to a major role for genetic susceptibility. Certain alleles of IL-4,10 and of the IL-4 receptor,11 are associated with more severe disease, and promoter variants of IL-10, IL-9, and TNF-α genes likely also influence disease severity.12 Variations ...

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