Targeting Herpes Simplex Virus-1 gD by a DNA Aptamer Can Be an Effective New Strategy to Curb Viral Infection

Abstract

Herpes simplex virus type 1 (HSV-1) is an important factor for vision loss in developed countries. A challenging aspect of the ocular infection by HSV-1 is that common treatments, such as acyclovir, fail to provide effective topical remedies. Furthermore, it is not very clear whether the viral glycoproteins, required for HSV-1 entry into the host, can be targeted for an effective therapy against ocular herpes in vivo. Here, we demonstrate that HSV-1 envelope glycoprotein gD, which is essential for viral entry and spread, can be specifically targeted by topical applications of a small DNA aptamer to effectively control ocular infection by the virus. Our 45-nt-long DNA aptamer showed high affinity for HSV-1 gD (binding affinity constant [Kd] = 50 nM), which is strong enough to disrupt the binding of gD to its cognate host receptors. Our studies showed significant restriction of viral entry and replication in both in vitro and ex vivo studies. In vivo experiments in mice also resulted in loss of ocular infection under prophylactic treatment and statistically significant lower infection under therapeutic modality compared to random DNA controls. Thus, our studies validate the possibility that targeting HSV-1 entry glycoproteins, such as gD, can locally reduce the spread of infection and define a novel DNA aptamer-based approach to control HSV-1 infection of the eye.

Мodern Approaches to the Treatment and Prevention of Recurrent of Ophthalmic Herpes. Review

“…В другом исследовании положительный противовирусный результат in vivo и ex vivo получен при медленном освобождении пептида G2 с применением контактной линзы [77]. Эффективным противовирусным действием обладает аптамер ДНК или РНК, который связывается с гликопротеином gD клеточной оболочки вируса, что приводит к снижению распространения вируса как в уже инфицированных клетках, так и на этапе их инфицирования [78].…”

Aptamer: A Versatile Probe in Medical Diagnosis

“…HIV-TAT peptide detection was also carried out on the carbon nanotube modified electrode with its particular aptamer [18]. HSV is one of the main causes of infectious illness, aptamers generated against HSV were used to detect the HSV at an earlier stage [1,19]. Furthermore, RNA aptamers selected against the HPV-16 E7 oncoprotein were proved for the detection of HPV associated cervical cancer [16].…”

Prior inhibition of AKT phosphorylation by BX795 can define a safer strategy to prevent herpes simplex virus-1 infection of the eye

“…Millions of patients around the world suffer from recurring HSV-1 infections, which can cause irreversible corneal scarring and potential need for corneal transplantation (7)(8)(9)(10)(11). HSV-1 has a seroprevalence of 60-90% with almost 100% of people infected by the age of 70 (12)(13)(14)(15).…”