Tannic acid modified silver nanoparticles show antiviral activity in herpes simplex virus type 2 infection.

Piotr Orlowski,Malgorzata Krzyzowska,Zuzanna Nowak,Marianna Gniadek,Mikolaj Donten,Piotr Baska,Grzegorz Celichowski,Julita Nowakowska,Jaroslaw Grobelny,Justyna Sokolowska,Emilia Tomaszewska

doi:10.1371/journal.pone.0104113

Abstract

The interaction between silver nanoparticles and herpesviruses is attracting great interest due to their antiviral activity and possibility to use as microbicides for oral and anogenital herpes. In this work, we demonstrate that tannic acid modified silver nanoparticles sized 13 nm, 33 nm and 46 nm are capable of reducing HSV-2 infectivity both in vitro and in vivo. The antiviral activity of tannic acid modified silver nanoparticles was size-related, required direct interaction and blocked virus attachment, penetration and further spread. All tested tannic acid modified silver nanoparticles reduced both infection and inflammatory reaction in the mouse model of HSV-2 infection when used at infection or for a post-infection treatment. Smaller-sized nanoparticles induced production of cytokines and chemokines important for anti-viral response. The corresponding control buffers with tannic acid showed inferior antiviral effects in vitro and were ineffective in blocking in vivo infection. Our results show that tannic acid modified silver nanoparticles are good candidates for microbicides used in treatment of herpesvirus infections.

Highlights

Herpes simplex virus (HSV) causes a contagious infection affecting approximately 60% to 95% of adults worldwide
Colloids stability confirmed by a Dynamic Light Scattering technique (DLS) test performed after one and six months from the initial date of synthesis showed that the measured size of nanoparticles was constant within the measurement error
Most of the evidence about the role of sexually transmitted diseases (STDs) in the transmission and control of HIV is focused on HSV-2 [28,38]

Summary

Introduction

Herpes simplex virus (HSV) causes a contagious infection affecting approximately 60% to 95% of adults worldwide. In the majority of infected individuals, HSV establishes latency in the neural ganglia, where it can be reactivated causing recurrent disease [1,2,3,4]. Genital HSV-2 infection is more common in women than in men. We may assume that ulcerations resulting from recurrent HSV-2 infection consist one of the most common factors influencing integrity and functioning of the vaginal mucosa [4,5]. There are many experimental anti-HSV-1 and anti-HSV2 vaccines, but none of them has been introduced into treatment of herpes infections

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