Novel approaches in fighting herpes simplex virus infections

Abstract

The development of novel strategies to eradicate herpes simplex virus (HSV) is a global public health priority. While acyclovir and related nucleoside analogues provide successful modalities for treatment and suppression, HSV remains highly prevalent worldwide and is a major cofactor fueling the HIV epidemic. HSV is the predominant cause of genital ulcerative disease, and neonatal and sporadic infectious encephalitis. Asymptomatic shedding, which occurs more frequently than previously appreciated, contributes to viral transmission. Acyclovir resistance may be problematic for immunocompromised patients and highlights the need for new safe and effective agents. Ideally, vaccines to prevent infection, drugs to inhibit the establishment of or reactivation from latency, or vaginal microbicides to prevent sexual and perinatal transmission are needed to control the epidemic. This review summarizes current therapeutic options and strategies in development. Keywords acyclovir; herpes simplex virus; microbicide; vaccineThe discovery of acyclovir (ACV), a nucleoside analogue that is selectively phosphorylated by herpes simplex virus (HSV) and inhibits viral replication by acting as a substrate for viral DNA polymerase, ushered in a new era in antiviral chemo therapy [1,2]. Despite the overwhelming success of ACV and related drugs, HSV remains a major global health problem, and is the leading cause of encephalitis and genital ulcerative disease, and a major cofactor for HIV infection. This reflects, in part, the ability of the virus to uniformly establish latency, reactivate frequently and to be horizontally and vertically transmitted during periods of

Enhancement of Antiviral Activity of Human Alpha-Defensin 5 against Herpes Simplex Virus 2 by Arginine Mutagenesis at Adaptive Evolution Sites

“…To obtain insight into the mechanism, we studied the binding of peptides to HSV-2 glycoprotein D (gD). Glycoprotein D is one of the essential molecules for HSV binding to and penetration of cells, especially for viral entry (1). Therefore, we examined the ability of HD5 analogs to interact with recombinant gD from HSV-2 using DPI.…”

“…Interestingly, to interpret how the peptides block virus entry to target cells, we conducted DPI assays, which first disclosed that HD5 analogs interacted with viral capsid protein gD at different affinities. HSV entry is a complex process that requires the concerted activities of gB, gD, and hetero-oligomers of glycoproteins H and L (gH-gL) (1). Because all of the capsid proteins of HSV are glycosylated and HD5 is a lectin that binds O-linked and N-linked glycans (36), it seems plausible that HD5 analogs may also bind other essential glycoproteins.…”

“…erpes simplex virus (HSV) is highly prevalent worldwide and plays an important role in fueling the human immunodeficiency virus (HIV) epidemic (1). In the United States, the seroprevalences of HSV-1 and HSV-2 infection have been estimated to be approximately 50% and 20%, respectively (2).…”

The Inflammatory Response to Viral Infection of the Central Nervous System

“…Herpes simplex viruses are the most common viral cause of encephalitis and are readily treatable with nucleoside analogues such as acyclovir. However, resistance has been observed leading to the development of alternatives such as helicase inhibitors and TLR agonists (Grauer et al, 2008;Wilson et al, 2009). Nitric oxide inhibitors have been suggested as a possible therapy in HIV to inhibit BBB disruption during HIV encephalopathy (Giovannoni et al, 1998).…”

Virus Infection and Type I Interferon in Endometriosis

“…CMV maintains latency in monocytes and macrophages. HSV-1 and HSV-2 can cause encephalitis and genital ulcerative disease (Wilson et al, 2009). The HSVs maintain latency in neuronal cells.…”