Mechanism of Anti-virus Activity of Houttuynia Cordata and The Role of miR-27a* in Herpes Simplex Virus Infection
Date Issued
2015
Date
2015
Author(s)
Hung, Pei-Yun
Abstract
Herpes simplex virus (HSV), a common latent virus in humans, causes certain severe diseases. Extensive use of acyclovir (ACV) results in the development of drug-resistant HSV strains, hence, there is an urgent need to develop new drugs to treat HSV infection. Houttuynia cordata (H. cordata), a natural herbal medicine, has been reported to exhibit anti-HSV effect which is partly NF-κB-dependent. However, the molecular mechanisms by which H. cordata inhibits HSV infection are not elucidated thoroughly. In this study, we found that H. cordata water extract (HCWE) inhibited the infection of HSV-1, HSV-2, and acyclovir-resistant HSV-1, mainly via blocking viral binding and penetration in the beginning of infection. HCWE also suppressed HSV replication. Furthermore, HCWE attenuated the first-wave of NF-κB activation, which is essential for viral gene expression. Further analysis of six compounds identified in H. cordata revealed that quercetin and isoquercitrin inhibit NF-κB activation and additionally, quercetin also has an inhibitory effect on viral entry. These results indicate that H. cordata could inhibit HSV infection through multiple mechanisms and could be a potential lead for development of new drugs for treating HSV. Recently, the microRNA also can be the antiviral target. MicroRNA is a class of small non-protein-coding RNAs that may act via endogenous RNA interference. However, few studies have explored the role of microRNA in HSV infection. In this study, we used the monocytic cell line THP1 and found that the expression of miR-27a* in THP1 was reduced after HSV-1 infection. Potential target genes of miR-27a* were predicted by the target prediction program, miRanda. One of the predicted targets is paired immunoglobulin-like type 2 receptor α (PILRα), the co-receptor of HSV-1, which contains an immunoreceptor tyrosine-based inhibition motif (ITIM) and can deliver inhibitory signals in immune cells. We hypothesized that HSV-1 infection could down-regulate the expression of miR-27a* and increase the expression of PILRα and then inhibit the antiviral immunity. Further studies showed that overexpression of miR-27a* in cells could significantly inhibit virus replication and also could increase the expression of TNF-α, IFN-β, and IL-6. Similar results were also observed by delivering PILRα-specific siRNA. Collectively, miR-27a* had important role in regulating innate antiviral immunity by inhibiting the expression of PILRα. Further studies will be required to elucidate the role of PILRα in HSV-1 infection.
Subjects
Herpes simplex virus
Houttuynia cordata
microRNA
SDGs
Type
thesis