MicroRNA profile in patients with chronic hepatitis b virus (CHBV) and human immunodeficiency virus (HIV) co-infection in a high prevalence setting.

Abstract

Introduction: HBV and HIV/HBV co-infection are significant public health issues, despite the availability of an effective HBV vaccine for nearly three decades. HBV and HIV both modulate microRNA (miRNA) expression to support viral replication. It has been estimated that 2.7 million people are co-infected with HBV and HIV worldwide. South Africa is an endemic setting for HBV and HIV infections. MiRNAs are small single-stranded non-coding RNAs that bind to the complementary strand of messenger RNA and suppress translation at the post-transcriptional level. The role played by miRNAs in HBV replication and pathogenesis is being increasingly recognized. This retrospective study aimed to describe the pattern of miRNA expression in patients coinfected with chronic HBV and HIV with varying disease severity, as indicated by HBeAg status, HBV viral load, ALT levels, and HIV viral load. Methods: Plasma miRNAs, specific to HBV, were measured by reverse-transcription quantitative polymerase chain reaction (qRT-PCR) in HBV and HIV negative healthy controls (n = 23) and patients coinfected with chronic HBV-HIV (n = 50). Samples from HBV-HIV coinfected patients were obtained from a previous study and controls were randomly selected from samples submitted for routine hepatitis and HIV serology at the Department of Virology, Inkosi Albert Luthuli Central Hospital. The studied miRNAs included hsa-miR-15b-5p, hsa-miR-20a-5p, hsa-miR-29a-3p, hsa-miR-122-5p, hsa-miR-125b-5p, hsa-miR-181b-5p, hsa-miR-192-5p, hsa-miR-193b-3p, hsa-miR-194-5p, and U6 snRNA (endogenous control). MiRNA expression levels were measured and compared between patients with high vs low HBV viral load, HBeAg positive vs HBeAg negative, high vs low ALT levels, and high vs low HIV viral load. Additionally, HBV viral load, ALT levels, and HIV viral load were correlated with miRNA expression levels. Results: The healthy control group consisted of 69.9% females while the chronic HBV-HIV coninfected group had 42% of females. Significantly higher expression levels of our HBV-specific miRNAs were observed in chronic HBV-HIV coinfected samples compared to healthy controls. Samples with high HBV viral load had significantly higher expression levels of hsa-miR-122-5p (p = 0.0001), hsa-miR-192-5p (p = 0.0003), and hsa-miR-193b-3p (p = 0.0002) compared to samples with low HBV viral load. In HBeAg-negatives samples, significantly higher levels of hsa-miR-15b-5p (p = 0.0054) and hsa-miR-181b-5p (p = 0.03) were observed compared to HBeAg-positive samples. No significant differences were observed in low vs high ALT levels and low vs high HIV viral load samples. A significant moderate positive correlation was observed between HBV viral load and the expression levels of hsa-miR-122-5p, hsa-miR-192-5p, and hsa-miR-193-3p. Conclusion: Our study provides evidence for the potential use of hsa-miR-15b-5p, hsa-miR-122-5p, hsa-miR-181b-5p, hsa-miR-192-5p and has-miR-193b-3p as additional or confirmatory tests, together with currently available prognostic and diagnostic markers in chronic HBV disease progression.