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Longitudinal transcriptomic characterization of the immune response to acute hepatitis C virus infection in patients with spontaneous viral clearance.

ABSTRACT: Most individuals exposed to hepatitis C virus (HCV) become persistently infected while a minority spontaneously eliminate the virus. Although early immune events influence infection outcome, the cellular composition, molecular effectors, and timeframe of the host response active shortly after viral exposure remain incompletely understood. Employing specimens collected from people who inject drugs (PWID) with high risk of HCV exposure, we utilized RNA-Seq and blood transcriptome module (BTM) analysis to characterize immune function in peripheral blood mononuclear cells (PBMC) before, during, and after acute HCV infection resulting in spontaneous resolution. Our results provide a detailed description of innate immune programs active in peripheral blood during acute HCV infection, which include prominent type I interferon and inflammatory signatures. Innate immune gene expression rapidly returns to pre-infection levels upon viral clearance. Comparative analyses using peripheral blood gene expression profiles from other viral and vaccine studies demonstrate similarities in the immune responses to acute HCV and flaviviruses. Of note, both acute dengue virus (DENV) infection and acute HCV infection elicit similar innate antiviral signatures. However, while transient in DENV infection, this signature was sustained for many weeks in the response to HCV. These results represent the first longitudinal transcriptomic characterization of human immune function in PBMC during acute HCV infection and identify several dynamically regulated features of the complex response to natural HCV exposure.

SUBMITTER: Rosenberg BR

PROVIDER: S-EPMC6160227 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:In the United States Hepatitis C virus (HCV) viral clearance is estimated to range between 20 and 30%. The objective of this study was to estimate the frequency of HCV clearance and identify correlates of viral clearance among patients newly identified as HCV antibody positive in a large urban health system in Los Angeles, California. METHODS:We identified patients between November 2015 and September 2017 as part of a newly implemented HCV screening and linkage-to-care program at University of California Los Angeles (UCLA) Health System. All patients were eligible for screening, though there were additional efforts to screen patients born between 1945 and 1965. We reviewed Medical records to categorize anti-HCV antibody positive patients as having spontaneously cleared HCV infection (HCV RNA not detected) or not (HCV RNA detected). We excluded those with a prior history of anti-HCV positivity or history of HCV treatment. We compared differences between those with and without detectable HCV RNA using chi-square test, Fisher's exact test, and t-test as appropriate. We assessed factors associated with HCV clearance using logistic regression analysis. RESULTS:Among the 320 patients included in this study, 56% were male. Baby boomers (52-72?years of age) comprised the single largest age group (62%). We found spontaneous HCV clearance in 58% (n?=?185). HCV viral clearance was slightly higher among women as compared to men (63% vs. 53%; p value?=?0.07) and varied by race/ethnicity: clearance among Blacks/African Americans was 37% vs. 58% among whites (p value?=?0.02). After adjusting for age, race/ethnicity, and sex we found that those diagnosed with chronic kidney disease had a tendency of decreased HCV viral clearance (adjusted OR?=?0.34; 95% CI 0.14-1.03). CONCLUSION:Of those patients newly identified as anti-HCV positive, 58% had cleared HCV virus, while the rest showed evidence of active infection. In addition, we found that clearance varied by race/ethnicity and clinical characteristics.

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Longitudinal transcriptomic characterization of the immune response to acute hepatitis C virus infection in patients with spontaneous viral clearance.

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