Chapter 40 : Human Susceptibility and Response to Viral Diseases

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Host genetic variation in components of both specific and innate immune responses affects susceptibility to viral infections. Innate immunity provides the first line of defense, and the development of adaptive immunity is stimulated by innate responses. Pathogen recognition receptors (PRRs) initiate signaling pathways that result in the production of antiviral interferons and cytokines. Mutations or genetic variants (polymorphisms) have been recognized in several factors of innate immunity. Notably, human populations from distinct geographic areas have different frequencies of immune gene variants. The genetic susceptibility may vary from life-threatening manifestations of specific virus infections to a moderately increased frequency of nonsevere infections. Although the innate immunity is nonspecific by nature, the reactions are stereotypic for viral infections compared with bacterial infections. Even infections caused by specific viruses can be differentiated from each other based on the innate immune response. Host response pattern determination by expression analysis of a predefined set of genes is a novel strategy in the diagnosis of virus infections. Another strategy in differentiating viral and bacterial infections from each other could be the determination of a single marker, such as myxovirus resistance protein A (MxA), which is generally induced by viruses but not by bacteria. Host response analysis could also be used in monitoring infections and antiviral treatment, but applications for routine use are not yet available. Certain host gene variants correlate with the prognosis of infection. Currently, for instance, interleukin (IL) 28B genotyping is used to aid in hepatitis C treatment decisions.

Citation: Peltola V, Ilonen J. 2016. Human Susceptibility and Response to Viral Diseases, p 567-578. In Loeffelholz M, Hodinka R, Young S, Pinsky B (ed), Clinical Virology Manual, Fifth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819156.ch40
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Myxovirus resistance protein A (MxA) blood levels in children 1 to 24 months of age according to virus detection and the presence of respiratory tract infection symptoms and in asymptomatic adults ( of subjects per group in parentheses). Respiratory viruses were diagnosed by reverse transcription real-time PCR for rhinovirus, enteroviruses, and respiratory syncytial virus (RSV) and by Seeplex RV12 multiplex PCR assay (Seegene, Seoul, Korea) for rhinovirus; RSV types A and B; adenovirus; influenza A and B viruses; parainfluenza virus types 1, 2, and 3; human metapneumovirus; and coronaviruses 229E/NL63 and OC43/HKU1. The boxes show median and interquartile range, and the whiskers show 10th and 90th percentiles. Percentages of measurements above the cut-off level of 175 micrograms per liter (dash line) are shown above the groups. (Reproduced from the with permission of the original publisher [ ].)

Citation: Peltola V, Ilonen J. 2016. Human Susceptibility and Response to Viral Diseases, p 567-578. In Loeffelholz M, Hodinka R, Young S, Pinsky B (ed), Clinical Virology Manual, Fifth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819156.ch40
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Image of FIGURE 2

Transcriptional profiling of host response in the diagnosis of certain viral and bacterial infections. Patients had various types of acute bacterial infections, respiratory viral infections, or dengue. Expression levels of functionally related sets of genes are displayed on a grid, with the coordinates corresponding to 1 of 28 module IDs (e.g., Module M3.1 is at the intersection of the third row and first column). Mapping transcriptional changes at the module level identifies disease-specific biosignatures in patients with infectious diseases. Expression levels were compared between patients and appropriately matched healthy controls on a module-by-module basis. The spots represent the percentage of significantly overexpressed (red) or underexpressed (blue) transcripts within a module (i.e., set of coordinately expressed genes). Blank spots indicate that there are no differences in the genes included in that module between patients and healthy controls. Each pathogen induces a disease-specific biosignature that is easily identifiable. (Reproduced from with permission of the original publisher [ ].

Citation: Peltola V, Ilonen J. 2016. Human Susceptibility and Response to Viral Diseases, p 567-578. In Loeffelholz M, Hodinka R, Young S, Pinsky B (ed), Clinical Virology Manual, Fifth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819156.ch40
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Examples of human genetic variants leading to susceptibility to or protection against viral infections

Citation: Peltola V, Ilonen J. 2016. Human Susceptibility and Response to Viral Diseases, p 567-578. In Loeffelholz M, Hodinka R, Young S, Pinsky B (ed), Clinical Virology Manual, Fifth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819156.ch40

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