Chapter 30 : Pathology and Pathogenesis of Virus Infections

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While the term immunopathology was originally used to describe an aberrant immune response to autoantigen resulting in pathology, more recent developments in our understanding of virus-induced immunopathology have revealed that this can be linked to both an aberrant immune response to the virus itself as well as unfavorable virus-induced changes to the immune response as a whole; for example, lymphopenia following certain types of infections as well as the specific loss of CD4 T cells in HIV infection. Perhaps the most common virus-induced pathology is T-cell-induced destruction of host tissues. T-cell mediated pathologies occur through both direct and indirect mechanisms including the targeted cytolysis of the infected cell by effector T cells, the induction of apoptosis in infected cells and generalized tissue damage due to bystander effects of T-cell activation. Difficulties in establishing an animal model of hantavirus pulmonary syndrome (HPS) had greatly hampered progress in understanding the factors involved in pathogenesis. Perhaps the most widely examined example of antibody dependent enhancement (ADE) can be found in dengue virus infections. The process by which viruses may induce or enhance autoimmunity is hypothesized to occur by a number of mechanisms. Recent clinical trials for several different vaccines, where vaccinated groups had elevated risk for infection and or disease than their naive cohorts, have highlighted the necessity for continued basic science research into the precise mechanisms of virus-induced immunopathology. One example of this can be found in the vastly different outcomes achieved with different strategies in respiratory syncytial virus (RSV) vaccination.

Citation: Jones C, Von Herrath M. 2011. Pathology and Pathogenesis of Virus Infections, p 383-389. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch30
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Image of FIGURE 1

Model of antibody-dependent enhancement of viral infection. In the absence of antibody, receptors on the surface of the virion attach to the cell via interactions with the cognate receptor on the surface of the cell, followed by adsorption of the virus into the host cell (A). In the presence of sufficient concentration of neutralizing antibody, viral adsorption or attachment of the virus to the cell is blocked (B). The presence of subneutralizing (either heterotypic or insufficient titer of neutralizing) preexisting antibody may enhance viral attachment or adsorption to the surface of Fc-receptor bearing cells. Alternatively, the simultaneous engagement Fc receptors on the surface of an infected cell may enhance the ability of the virus to replicate in Fc receptor bearing cells downstream of attachment and adsorption or alter the function of the infected APC (C).

Citation: Jones C, Von Herrath M. 2011. Pathology and Pathogenesis of Virus Infections, p 383-389. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch30
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Examples of host and viral factors contributing to virus induced pathology

Citation: Jones C, Von Herrath M. 2011. Pathology and Pathogenesis of Virus Infections, p 383-389. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch30

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