Ocular HSV-1 latency, reactivation and recurrent disease.
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.
Toma
Hassanain S
HS
Louisiana State University Health Sciences Center, New Orleans, LA 70112-2234, USA.
Murina
Andrea T
AT
Areaux
Raymond G
RG
Neumann
Donna M
DM
Bhattacharjee
Partha S
PS
Foster
Timothy P
TP
Kaufman
Herbert E
HE
Hill
James M
JM
D000818:Animals; D004195:Disease Models, Animal; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D016849:Keratitis, Herpetic / Q000517:prevention & control / Q000821:virology*; D012008:Recurrence; D014775:Virus Activation / Q000502:physiology*; D017735:Virus Latency / Q000502:physiology*