Ocular HSV-1 Latency, Reactivation and Recurrent Disease

Abstract

Ocular infection with HSV-1 continues to be a serious clinical problem despite the availability of effective antivirals. Primary infection with HSV-1 can involve ocular and adenaxial sites and can manifest as blepharitis, conjunctivitis, or corneal epithelial keratitis. After initial ocular infection, HSV-1 can establish latent infection in the trigeminal ganglia for the lifetime of the host. During latency, the viral genome is retained in the neuron without producing viral proteins. However, abundant transcription occurs at the region encoding the latency-associated transcript, which may play significant roles in the maintenance of latency as well as neuronal reactivation. Many host and viral factors are involved in HSV-1 reactivation from latency. HSV-1 DNA is shed into tears and saliva of most adults, but in most cases this does not result in lesions. Recurrent disease occurs as HSV-1 is carried by anterograde transport to the original site of infection, or any other site innervated by the latently infected ganglia, and can reinfect the ocular tissues. Recurrent corneal disease can lead to corneal scarring, thinning, stromal opacity and neovascularization and, eventually, blindness. In spite of intensive antiviral and anti-inflammatory therapy, a significant percentage of patients do not respond to chemotherapy for herpetic necrotizing stromal keratitis. Therefore, the development of therapies that would reduce asymptomatic viral shedding and lower the risks of recurrent disease and transmission of the virus is key to decreasing the morbidity of ocular herpetic disease. This review will highlight basic HSV-1 virology, and will compare the animal models of latency, reactivation, and recurrent ocular disease to the current clinical data.

HSV carrying WT REST establishes latency but reactivates only if the synthesis of REST is suppressed

“…In brief, peripheral ganglia may be viewed as barriers to the spread of viruses via neurons from the peripheral tissues of the CNS. The hypothesis predicts that neurons, like other cells in the body, possess the innate immune mechanisms to respond to the presence of viruses in ways designed to block their replication (35)(36)(37)(38). The hypothesis envisions that one such mechanism is the expression of HCLR repressor complex (3,21,22,24,25,(39)(40)(41).…”

Ocular Sustained Release Nanoparticles Containing Stereoisomeric Dipeptide Prodrugs of Acyclovir

“…The structures of the intermediate and final compounds were confirmed by 1 H NMR and mass spectrometry. 1 H NMR was carried out using a Varian-400 MHz NMR spectrometer. Chemical shifts were expressed in parts per million (ppm) relative to the solvent signal (CD 3 OD, 3.31ppm for proton) using tetramethylsilane as an internal standard.…”

“…Intermittent corneal infections can lead to corneal thinning, scarring, stromal opacity, and ultimately, blindness. 1,2 Previous studies demonstrate that patients infected with HSV-1 have a 50% chance of recurrence. 3 Herpes simplex keratitis is characterized by rapid spread of virus deep into the cornea and develops into a more severe infection called stromal keratitis, which renders the body's immune system attack and destroy stromal cells.…”

Unilateral Posterior Interstitial Keratitis as a Clinical Presentation of Herpes Simplex Virus Disease

“…The extended duration of this disease has not been fully explained, but some have hypothesized long-term viral antigen persistence in the corneal stroma. 7,8 CD4 + T cells have been implicated as primary mediators of the immune response. Although HSV interstitial keratitis was at one time treated with topical antivirals, most corneal specialists now treat this disease with a combination of oral antivirals and topical corticosteroids to both resolve active corneal inflammation and reduce the risk of disease recurrence.…”