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Updated: Mar 11, 2026
Two Methods of Heterokaryon Formation to Discover HCV Restriction Factors
Published on: July 16, 2012
Identification of the transcripts associated with spontaneous HCV clearance in individuals co-infected with HIV and
Yue Chen1, Chengli Shen2, Debjani Guha2
1Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, 2138 Parran Hall, 130 DeSoto Street, Pittsburgh, Pa, 15261, USA. cheny@pitt.edu.
Insights
Individuals who spontaneously clear hepatitis C virus (HCV) infection alongside human immunodeficiency virus (HIV) show distinct plasma gene expression patterns. These patterns, linked to innate immunity, may explain spontaneous HCV clearance in co-infected patients.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Human immunodeficiency virus (HIV) impacts hepatitis C virus (HCV) infection outcomes.
- While many co-infected individuals develop chronic HCV, a significant portion spontaneously clear the virus.
- The mechanisms behind spontaneous HCV clearance remain largely unknown.
Purpose of the Study:
- To investigate differential gene expression in HIV/HCV co-infected subjects with persistent versus cleared HCV infection.
- To identify potential molecular mechanisms underlying spontaneous HCV clearance.
Main Methods:
- Plasma RNA sequencing was performed on HIV/HCV co-infected subjects who cleared HCV and those with chronic infection.
- Differential gene expression analysis was conducted to identify transcripts associated with HCV clearance.
Main Results:
- Significantly elevated plasma mRNA levels were identified in subjects who cleared HCV prior to infection (at least 5-fold, FDR <0.05).
- Twelve genes were uniquely upregulated in the clearance group before HCV infection.
- Upregulated genes and their regulators are associated with innate immune response functions.
Conclusions:
- Spontaneous HCV clearance in co-infected individuals may be associated with the expression of specific genes involved in innate immunity.
- These findings offer insights into the host response mechanisms governing HCV viral control.
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.
