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Chapter 11 : Plasticity of the Hepatitis C Virus Genome

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Plasticity of the Hepatitis C Virus Genome, Page 1 of 2

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Abstract:

With approximately 3% of the world's population (~130 million people) infected with hepatitis C virus (HCV), the World Health Organization has declared HCV a global health problem. The genotypes are divided into multiple epidemiologically distinct subtypes differing by 20 to 25% from one another. In public databases, the consensus sequence of the quasispecies is normally presented as the most predominant residue at any given position. Virtually all patients undergo reinfection of the donor organ. This reinfection is associated with a dramatic shift in the complexity of the quasispecies population, suggesting that only a limited number of viral variants establish reinfection. Importantly, the sequences from the infection source are located close to the center of the phylogenetic tree whereas the viruses from different patients continuously evolve away from the center. It is noteworthy that samples for the subsequent infection of the next animal were taken during the acute phase before antibodies became detectable. In a study it was found that a virus harboring an escape mutation in an HLA-B8 restricted epitope in NS3 was transmitted to a host who was HLA-B8 negative and therefore was not able to mount the same T-cell response.

Citation: Timm J, Roggendorf M. 2012. Plasticity of the Hepatitis C Virus Genome, p 178-190. In Hacker J, Dobrindt U, Kurth R (ed), Genome Plasticity and Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817213.ch11
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Image of FIGURE 1
FIGURE 1

Phylogenetic tree depicting HCV sequences retrieved from the HCV sequence database. HCV sequences fall into seven different clusters (genotypes 1 through 7) and are further classified into subtypes.

Citation: Timm J, Roggendorf M. 2012. Plasticity of the Hepatitis C Virus Genome, p 178-190. In Hacker J, Dobrindt U, Kurth R (ed), Genome Plasticity and Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817213.ch11
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Image of FIGURE 2
FIGURE 2

Organization of the HCV genome and polyprotein. The HCV genome is an RNA molecule of approximately 9,600 nucleotides structured in a coding region that contains one large open reading frame and is flanked by nontranslated regions at the 5′ and 3′ ends. The polyprotein is cleaved into structural (core, envelope 1, and envelope 2) and nonstructural (NS2, NS3, NS4A, NS4B, NS5A, and NS5B) proteins with one additional small protein at the junction between the structural and nonstructural elements (p7 protein).

Citation: Timm J, Roggendorf M. 2012. Plasticity of the Hepatitis C Virus Genome, p 178-190. In Hacker J, Dobrindt U, Kurth R (ed), Genome Plasticity and Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817213.ch11
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Image of FIGURE 3
FIGURE 3

Phylogenetic tree of sequences from a large HCV genotype 1b outbreak. The red sequences are clonal sequences from the infection source and represent the quasispecies population of the inoculum. The black sequences are bulk sequences derived from different patients 30 years after infection from this common source.

Citation: Timm J, Roggendorf M. 2012. Plasticity of the Hepatitis C Virus Genome, p 178-190. In Hacker J, Dobrindt U, Kurth R (ed), Genome Plasticity and Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817213.ch11
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Image of FIGURE 4
FIGURE 4

HLA class I-associated evolution in an HLA-B35-restricted CD8 epitope in a large HCV genotype 1b outbreak. Viral sequences are aligned with a consensus sequence and sorted into sequences derived from HLA-B35-positive and HLA-B35-negative subjects. Differences from the consensus sequence are significantly more frequent in HLA-B35-positive subjects (< 0.001).

Citation: Timm J, Roggendorf M. 2012. Plasticity of the Hepatitis C Virus Genome, p 178-190. In Hacker J, Dobrindt U, Kurth R (ed), Genome Plasticity and Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817213.ch11
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Image of FIGURE 5
FIGURE 5

Entropy across the HCV polyprotein. All HCV genotype 1b sequences were retrieved from the Los Alamos National Laboratory HCV Sequence Database. The entropy score was calculated for all windows of 20 residues.

Citation: Timm J, Roggendorf M. 2012. Plasticity of the Hepatitis C Virus Genome, p 178-190. In Hacker J, Dobrindt U, Kurth R (ed), Genome Plasticity and Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817213.ch11
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