Expression of microRNAs in the detection and therapeutic roles of viral infections: Mechanisms and applications

Abstract

In recent years, microRNAs (miRNAs) are potential diagnostic and therapeutic agents for viral infections. Here, we aimed to investigate the expression of microRNAs in the identification and treatment of viral infections. MiRNAs are non-coding molecules that control gene expression and participate in numerous biological processes, including host immunity and pathogen duplication. MiRNAs have played a role in the pathogenesis of various viral infections, such as HIV and HCV. Their presence in the tissues and serum of infected patients has been demonstrated to help predict disease progression, identify disease subtypes, and evaluate treatment responses. Research has shown that miRNAs can detect viral infections by identifying specific miRNAs in serum. For example, miRNA expression profiling was recently used to distinguish between hepatitis C and hepatitis B viral infections precisely. Furthermore, miRNAs can be used to detect the presence of multiple viral infections simultaneously by assessing the expression levels of these miRNAs. Also, miRNAs can differentiate between different genetic variants of the same virus, which is useful for identifying emerging viral strains or drug-resistant ones. MiRNAs have been identified as being a factor in treating viral infections. For example, miRNA mimics have decreased gene expression and halted viral replication in HIV, HCV, and EBV. Moreover, microRNA antagonists have been utilized to inhibit pro-inflammatory cytokines, thereby modulating the immune response and the severity of infections.

Keywords: Barr virus; Epstein; Hepatitis B; Hepatitis C; Human immunodeficiency virus; MicroRNA.

Fig. 1

Types of microRNAs involved in hepatitis B and hepatitis C virus infections; In Figure (a), microRNAs whose expression decreases under the influence of hepatitis C (including miR-125, miR-146a) and microRNAs whose expression increases in liver cancer tissue (miR-21, miR- 122, miR-130b, miR-146a, miR-155, miR-196a, miR-373) and in Figure (b), the microRNAs whose expression changes under the influence of hepatitis virus have been identified, which are in the order of microRNA mir-372, miR-373 and miR-21 expression increases and let-7 and miR-122 expression decreases. These changes help in timely diagnosis of infection caused by these viruses; For example, miR-21 and miR-122 expression changes play an essential role in the early diagnosis of liver cirrhosis.

Fig. 2

MicroRNA expression changes in viral infections and their consequences; HIV infection increases the expression of miR-21, which activates the TLR7-dependent death pathway, which causes neurotoxicity (a). In infections caused by EBV, the expression of microRNAs of the miR-200 family, which play a role in inhibiting tumor progression and metastasis, is reduced. It is also known that members of miR-200 are involved in lytic reactivation in epithelial cells and lymphocytes. Infected B cells have a role, so that the reduction of the expression of this miRNA reduces the lytic reactivation (b). MicroRNA 122 is a specific liver microRNA that has the role of a tumor suppressor, which increases the infectivity of this virus by helping to stabilize the genome and accumulate the viral genome (c). In hepatitis B infection, an increase in miR-221, miR-222, miR-215, miR-21, miR-192 is observed, which causes a decrease in interleukin 21 produced by T lymphocytes (d).

Fig. 3

MicroRNAs involved in coxsackie virus infection, miR-9, which has an essential role in the formation and maturation of neural progenitor cells, and may play a role in inhibiting the growth of coxsackie and influenza viruses (a).^, MiR-21 increase by virus-infected cells inhibits the growth of coxsackie virus B3 and SARS-CoV-2 through the MAPK pathway and also inhibits the apoptosis of the involved cells (b). MicroRNA 141 plays an important role in suppressing metastasis and growth of HCC cells, and infection with Coxsackie B3 and influenza viruses increases the expression of miR-141, which accelerates inflammation and leads to oxidative stress (c).