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Chapter 28 : Immunogenetics of the Host Response to Viral Infections

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Abstract:

This chapter reviews the main steps of the adaptive immune responses and discusses the consequences of genetic polymorphism for the susceptibility to viral infections. It also reviews recent important results obtained with particular viral infections of mice and of humans and concludes with some general remarks on the consequences of these studies for both our fundamental understanding of viral pathogenesis and practical applications to human medicine. Extensive polymorphism of class I and class II molecules, the number of alleles, and their heterozygosity account for the ability to mount efficient immune responses against a large variety of infectious agents. Nevertheless, the modulation of the immune response to viruses by the major histocompatibility complex (MHC) haplotype is well documented for mice and other laboratory animals. The genes and their protein products constitute one of the best-characterized systems of genetically regulated control of viral infections. Importantly, the effect of the gene on resistance was not mediated by the adaptive immune responses but was dependent on alpha/beta interferon. A better comprehension of the genetic control of virus infections will help us understand not only how we have evolved but also what we can and cannot achieve with antiviral drugs and vaccines.

Citation: Brahic M, Bureau J, Bangham C, Gachelin G. 2002. Immunogenetics of the Host Response to Viral Infections, p 421-436. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch28

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Major Histocompatibility Complex Class I
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Human immunodeficiency virus 1
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Murray valley encephalitis virus
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Figure 1

Summary of antigen presentation by the MHC class I and class II pathways. The class I pathway, present in all nucleated cells, is illustrated on the right, and the class II pathway, which is specific to antigen-presenting cells, is illustrated on the left. The T cell is at the top, and the presenting cell at the bottom. The asterisks denote the steps in the pathways of antigen processing and presentation in which host polymorphism might influence the specificity or efficiency of immune recognition. Polymorphism in the proteases involved in these pathways (i.e., the proteasomal, cytoplasmic, and endosomal proteases) might affect the repertoire of peptides generated from viral proteins.

Citation: Brahic M, Bureau J, Bangham C, Gachelin G. 2002. Immunogenetics of the Host Response to Viral Infections, p 421-436. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch28
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