Harringtonine Inhibits Herpes Simplex Virus Type 1 Infection by Reducing Herpes Virus Entry Mediator Expression.

Ye Liu,Qiao You,Zhiwei Wu,Zhenping Huang,Fang Zhang,Deyan Chen

doi:10.3389/fmicb.2021.722748

Abstract

Herpes simplex virus type 1 (HSV-1) infection induces various clinical disorders, such as herpes simplex encephalitis (HSE), herpes simplex keratitis (HSK), and genital herpes. In clinical intervention, acyclovir (ACV) is the major therapeutic drug used to suppress HSV-1; however, ACV-resistant strains have gradually increased. In the present study, harringtonine (HT) significantly inhibited infection of HSV-1 as well as two ACV-resistant strains, including HSV-1 blue and HSV-1 153. Time-of-drug addition assay further revealed that HT mainly reduced the early stage of HSV-1 infection. We also demonstrated that HT mainly affected herpes virus entry mediator (HVEM) expression as shown by qPCR, Western Blot, and Immunofluorescence. Collectively, HT showed antiviral activity against HSV-1 and ACV-resistant strains by targeting HVEM and could be a promising therapeutic candidate for mitigating HSV-1-induced-pathogenesis.

Highlights

Herpes simplex virus type 1 (HSV-1) is a double-stranded DNA virus belonging to Herpesvirus, spreading worldwide
HT showed higher antiviral activity for all five HSV-1 strains at the same concentration of ACV and HT than ACV. These results suggested that HT could efficiently inhibit HSV-1 infection
Our study demonstrated that HT had antiviral activities against five different HSV-1 strains, including two ACV-resistant strains

Summary

Introduction

Herpes simplex virus type 1 (HSV-1) is a double-stranded DNA virus belonging to Herpesvirus, spreading worldwide. The estimated prevalence of HSV-1 infection is 67% globally, ranging from 49 to 87% (Looker et al, 2015; Harris, 2019). The majority of HSV-1 infections occur during childhood by oral-oral contact (Gupta et al, 2007). Recurrent infections of HSV-1 can cause complications such as orofacial herpes, ocular lesions, genital diseases, and in severe cases, lethal encephalitis (Levitz, 1998; Kaye and Choudhary, 2006; Gupta et al, 2007). Acyclovir (ACV), introduced in 1977, is the first specific drug for HSV treatment by targeting viral DNA polymerase (Elion et al, 1977). ACV and its analogs remain the first-line treatment for the management of HSV-1 infection. The development of novel and potent antiviral treatment with different mechanisms is imminent (Jiang et al, 2016)

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Conclusion