Abstract

(1) Background: Lactoferrin has been recognized as a potent inhibitor of human herpetic viruses, such as herpes simplex type 1 (HSV-1) and 2 (HSV-2). In this work, we tested if silver and gold nanoparticles modified with lactoferrin (LF-Ag/AuNPs) can become novel microbicides with additional adjuvant properties to treat genital herpes infection. (2) Methods: The antiviral and cytotoxic activities of LF-Ag/AuNPs were tested in human skin HaCaT and vaginal VK-2-E6/E7 keratinocytes. Viral titers and immune responses after treatment with LF-Ag/AuNPs were tested in murine vaginal HSV-2 infection. (3) Results: LF-Ag/AuNPs inhibited attachment and entry of HSV-2 in human keratinocytes much better than lactoferrin. Furthermore, pretreatment with LF-AgNPs led to protection from infection. Infected mice treated intravaginally with LF-Ag/AuNPs showed lower virus titers in the vaginal tissues and spinal cords in comparison to treatment with lactoferrin. Following treatment, vaginal tissues showed a significant increase in CD8+/granzyme B + T cells, NK cells and dendritic cells in comparison to NaCl-treated group. LF-Ag/AuNPs-treated animals also showed significantly better expression of IFN-γ, CXCL9, CXCL10, and IL-1β in the vaginal tissues. (4) Conclusions: Our findings show that LF-Ag/AuNPs could become effective novel antiviral microbicides with immune-stimulant properties to be applied upon the mucosal tissues.

Highlights

  • Herpes simplex virus type 2 (HSV-2) is the primary cause of genital herpes and one of the most common sexually transmitted infections

  • UV–Vis spectroscopy was used for confirmation of NPs synthesis by observation of the characteristic localized surface plasmon resonance (LSPR) peak in UV–Vis spectra

  • The hydrodynamic size of nanoparticles and its colloidal stability were tested with DLS and

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Summary

Introduction

Herpes simplex virus type 2 (HSV-2) is the primary cause of genital herpes and one of the most common sexually transmitted infections. After establishing latency in the sacral ganglia, HSV-2 reactivates, leading to intermittent shedding of virus in the genital tract [1]. Antiviral drugs, which target viral DNA polymerase, can partially control the signs and symptoms of genital herpes when used to treat first clinical and recurrent episodes or when used as daily suppressive therapy. These drugs neither eradicate latent virus nor affect the risk, frequency, or severity of recurrences after the drug is discontinued [1]

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