Hepatitis C Virus Antigenic Convergence

被引:22
作者
Campo, David S. [1 ]
Dimitrova, Zoya [1 ]
Yokosawa, Jonny [1 ,2 ]
Duc Hoang [1 ,3 ]
Perez, Nestor O. [1 ,4 ]
Ramachandran, Sumathi [1 ]
Khudyakov, Yury [1 ]
机构
[1] Ctr Dis Control & Prevent, Mol Epidemiol & Bioinformat Lab, Div Viral Hepatitis, Atlanta, GA 30329 USA
[2] Univ Fed Uberlandia, Virol Lab, Inst Ciencias Biomed, BR-38400 Uberlandia, MG, Brazil
[3] Natl Inst Hyg & Epidemiol, Hanoi, Vietnam
[4] Probiomed SA, Tenancingo, Mexico
关键词
HYPERVARIABLE REGION 1; REACTIVE ANTIBODIES; SEQUENCE EVOLUTION; INFECTION; RESPONSES; DIVERSITY; VACCINATION; CHIMPANZEES; POPULATION; MIMOTOPES;
D O I
10.1038/srep00267
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
Vaccine development against hepatitis C virus (HCV) is hindered by poor understanding of factors defining cross-immunoreactivity among heterogeneous epitopes. Using synthetic peptides and mouse immunization as a model, we conducted a quantitative analysis of cross-immunoreactivity among variants of the HCV hypervariable region 1 (HVR1). Analysis of 26,883 immunological reactions among pairs of peptides showed that the distribution of cross-immunoreactivity among HVR1 variants was skewed, with antibodies against a few variants reacting with all tested peptides. The HVR1 cross-immunoreactivity was accurately modeled based on amino acid sequence alone. The tested peptides were mapped in the HVR1 sequence space, which was visualized as a network of 11,319 sequences. The HVR1 variants with a greater network centrality showed a broader cross-immunoreactivity. The entire sequence space is explored by each HCV genotype and subtype. These findings indicate that HVR1 antigenic diversity is extensively convergent and effectively limited, suggesting significant implications for vaccine development.
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页数:8
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