Chapter 12 : Human Genetic Factors Involved in Viral Pathogenesis

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This chapter reviews genetic traits associated with susceptibility and resistance to several RNA viruses. HIV is an enveloped retrovirus that has caused more than 25 million deaths worldwide. is a duplicated variant of (), and this chemokine is the most potent chemokine receptor 5 (CCR5) agonist and hence the most effective competitive inhibitor of R5 HIV-1 entry. Volunteer challenge studies have concluded that (i) nonsecretors are resistant to infection, (ii) susceptibility occurs despite repeated challenge with identical virus, and (iii) short-term protective immunity can develop. Studies from authentic outbreaks show that protection from symptomatic norovirus infection is strongly associated with the G428A nonsense mutation in . There are four different dengue virus serotypes circulating (1 to 4), each being able to cause both asymptomatic and severe disease. A study that compared the genotypes of 87 unrelated Thai children who had been hospitalized because of dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS) was followed and reviewed by others, of which several found associations with HLA class I genotypes and some also with an HLA class II antigen. There is limited information regarding human genetic susceptibility factors associated with tick-borne encephalitis virus (TBEV). An interesting example comes from the pharmacokinetics of an HIV medicine, in which abacavir, a nucleoside reverse transcriptase inhibitor, can induce hypersensitivity that limits its use. Investigators identified a particular HLA haplotype that greatly increases the risk of abacavir hypersensitivity.

Citation: Svensson L, Kindberg E. 2009. Human Genetic Factors Involved in Viral Pathogenesis, p 177-193. In Brasier A, García-Sastre A, Lemon S (ed), Cellular Signaling and Innate Immune Responses to RNA Virus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555815561.ch12
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Figure 1

Secretor status, the ability to express histo-blood group antigens on mucosa and in secretions, is determined by the gene. Individuals lacking a functional allele are so-called nonsecretors, and carriers of at least one functional allele are termed secretors. Secretor status also indirectly determines the Lewis phenotype. Nonsecretors with a functional FUT3 enzyme are Lewis a (Le a) positive and secretors are Lewis b (Le b) positive. Individuals lacking the FUT3 enzyme are so-called Lewis negative.

Citation: Svensson L, Kindberg E. 2009. Human Genetic Factors Involved in Viral Pathogenesis, p 177-193. In Brasier A, García-Sastre A, Lemon S (ed), Cellular Signaling and Innate Immune Responses to RNA Virus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555815561.ch12
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Figure 2

Electron micrograph of human norovirus in a clinical specimen.

Citation: Svensson L, Kindberg E. 2009. Human Genetic Factors Involved in Viral Pathogenesis, p 177-193. In Brasier A, García-Sastre A, Lemon S (ed), Cellular Signaling and Innate Immune Responses to RNA Virus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555815561.ch12
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Table 1

Genetic factors associated with resistance or predisposition to specific viral infections

Citation: Svensson L, Kindberg E. 2009. Human Genetic Factors Involved in Viral Pathogenesis, p 177-193. In Brasier A, García-Sastre A, Lemon S (ed), Cellular Signaling and Innate Immune Responses to RNA Virus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555815561.ch12
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Table 2

Influence of genetic variability on susceptibility to HIV infection and AIDS

Citation: Svensson L, Kindberg E. 2009. Human Genetic Factors Involved in Viral Pathogenesis, p 177-193. In Brasier A, García-Sastre A, Lemon S (ed), Cellular Signaling and Innate Immune Responses to RNA Virus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555815561.ch12

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