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Higher dN/dS ratios in the HCV core gene, but not in the E1/HVR1 gene, are associated with human immunodeficiency virus-associated immunosuppression

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Abstract

Coinfection with HCV and HIV is prevalent among former commercial blood donors in some rural areas in China. Genetic variability of the HCV core and E1/HVR1 was investigated in 23 patients chronically infected with HCV-1b, with or without concomitant HIV infection. Genetic variability in the core sequence was higher under HIV-associated immunocompromised conditions. Both the Shannon entropy values at each nucleotide position and the dN/dS values at each codon were statistically higher in HIV/HCV-coinfected patients with lower CD4+ T cell counts (p-values were <0.0001 and equal to 0.0372, respectively). The more significant difference of dN/dS value occurred in a specific subregion of the core gene that is enriched in CTL/Th epitopes (p = 0.0083). The dN/dS values of full-length core antigen were found to be negatively correlated with the S/CO ratio of plasma anti-HCV antibodies. By contrast, no significant difference in genetic diversity/complexity and dN/dS values in the E1/HVR1 region was found between those two groups. These results suggest that the dN/dS ratio in the core gene, but not in the E1/HVR1 gene, is influenced more by host CD4+ T cell–mediated cellular immunity.

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Acknowledgments

We are very grateful to all who provided blood samples for this study. We also thank Dr. Xiang He for his advice in data analysis and preparing this manuscript. This work was supported by grants from the National Science and Technology Major Project for Infectious Diseases (2012ZX10002003, 2012ZX10002005), the National Science Foundation of Beijing (7122108), and the Doctoral Program of Higher Education of China (20100001120047).

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The authors have declared that no competing interests exist.

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Authors and Affiliations

  1. Department of Microbiology, Peking University Health Science Center, Beijing, 100191, China

    Chun-Hui Xu, Tao Shen, Jia-Jia Zheng, Jing Tu & Feng-Min Lu

  2. Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan, China

    Wei-Dong Zhang

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  1. Chun-Hui Xu
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  2. Tao Shen
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  3. Jia-Jia Zheng
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  5. Wei-Dong Zhang
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Correspondence to Wei-Dong Zhang or Feng-Min Lu.

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Chun-Hui Xu and Tao Shen contributed equally to this work

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Xu, CH., Shen, T., Zheng, JJ. et al. Higher dN/dS ratios in the HCV core gene, but not in the E1/HVR1 gene, are associated with human immunodeficiency virus-associated immunosuppression. Arch Virol 157, 2153–2162 (2012). https://doi.org/10.1007/s00705-012-1390-z

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  • DOI: https://doi.org/10.1007/s00705-012-1390-z

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