Identification of the transcripts associated with spontaneous HCV clearance in individuals co-infected with HIV and HCV

Yue Chen*, Chengli Shen, Debjani Guha, Ming Ding, Scott Kulich, Aiymkul Ashimkhanova, Charles Rinaldo, Eric Seaberg, Joseph B. Margolick, Valentina Stosor, Otoniel Martínez-Maza, Phalguni Gupta

*Corresponding author for this work

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Background: Infection with human immunodeficiency virus (HIV) influences the outcome and natural disease progression of hepatitis C virus (HCV) infection. While the majority of HCV mono-infected and HCV/HIV co-infected subjects develop chronic HCV infection, 20-46% of mono- and co-infected subjects spontaneously clear HCV infection. The mechanism underlying viral clearance is not clearly understood. Analysis of differential cellular gene expression (mRNA) between HIV-infected patients with persistent HCV infection or spontaneous clearance could provide a unique opportunity to decipher the mechanism of HCV clearance. Methods: Plasma RNA from HIV/HCV co-infected subjects who cleared HCV and those who remained chronically infected with HCV was sequenced using Ion Torrent technology. The sequencing results were analyzed to identify transcripts that are associated with HCV clearance by measuring differential gene expression in HIV/HCV co-infected subjects who cleared HCV and those who remained chronically infected with HCV. Results: We have identified plasma mRNA, the levels of which are significantly elevated (at least 5 fold, False Discovery Rate (FDR) <0.05) before HCV infection in subjects who cleared HCV compared to those who remained chronically infected. Upon further analysis of these differentially expressed genes, before and after HCV infection, we found that before HCV infection 12 genes were uniquely upregulated in the clearance group compared to the chronically infected group. Importantly, a number of these 12 genes and their upstream regulators (such as CCL3, IL17D, LBP, SOCS3, NFKBIL1, IRF) are associated with innate immune response functions. Conclusions: These results suggest that subjects who spontaneously clear HCV may express these unique genes associated with innate immune functions.

Original languageEnglish (US)
Article number693
JournalBMC Infectious Diseases
Volume16
Issue number1
DOIs
StatePublished - Nov 22 2016

Keywords

  • Chronic HCV infection
  • Clearance of HCV infection
  • HIV/HCV coinfection
  • Plasma RNA sequencing
  • Sequence analysis

ASJC Scopus subject areas

  • Infectious Diseases

Fingerprint Dive into the research topics of 'Identification of the transcripts associated with spontaneous HCV clearance in individuals co-infected with HIV and HCV'. Together they form a unique fingerprint.

  • Cite this

    Chen, Y., Shen, C., Guha, D., Ding, M., Kulich, S., Ashimkhanova, A., Rinaldo, C., Seaberg, E., Margolick, J. B., Stosor, V., Martínez-Maza, O., & Gupta, P. (2016). Identification of the transcripts associated with spontaneous HCV clearance in individuals co-infected with HIV and HCV. BMC Infectious Diseases, 16(1), [693]. https://doi.org/10.1186/s12879-016-2044-7