No abstract

Herpes simplex virus type-1 (HSV-1) is a neurotropic, double-stranded DNA virus that can cause a wide variety of diseases, including many ocular pathologies. It is one of the leading causes of infectious blindness in the United States. Because of its ubiquitous nature and its potential to cause serious ocular maladies, there is a significant need for more effective antiviral therapies against ocular HSV-1. In this review, we discuss the lifecycle of HSV-1 as it pertains to corneal infections and the clinically approved as well as emerging treatments to combat HSV-1 infections. We also highlight some newly identified host targets for the antiviral drug development.

Herpes simplex virus (HSV) can infect a broad host range and cause mild to life threating infections in humans. The surface glycoproteins of HSV are evolutionarily conserved and show an extraordinary ability to bind more than one receptor on the host cell surface. Following attachment, the virus fuses its lipid envelope with the host cell membrane and releases its nucleocapsid along with tegument proteins into the cytosol. With the help of tegument proteins and host cell factors, the nucleocapsid is then docked into the nuclear pore. The viral double stranded DNA is then released into the host cell’s nucleus. Released viral DNA either replicates rapidly (more commonly in non-neuronal cells) or stays latent inside the nucleus (in sensory neurons). The fusion of the viral envelope with host cell membrane is a key step. Blocking this step can prevent entry of HSV into the host cell and the subsequent interactions that ultimately lead to production of viral progeny and cell death or latency. In this review, we have discussed viral entry mechanisms including the pH-independent as well as pH-dependent endocytic entry, cell to cell spread of HSV and use of viral glycoproteins as an antiviral target.