Herpes simplex virus DNA in corneal transplants: Prospective study of 38 recipients

Abstract

Herpes simplex virus (HSV) infection of the eye can induce epithelial and stromal keratitis and may also lead to postoperative endothelial failure in keratoplasty. Clinical symptoms and/or virus culture of corneal scrapings most frequently provide the basis for diagnosis of ocular HSV infection, and although HSV DNA has been shown to be present in the cornea, its role in success or failure of corneal grafts remains unclear. In this study, a PCR assay was used to detect HSV DNA in corneal buttons of 38 corneal graft recipients and in donor scleral remnants, retaining one-half of each sample for subsequent viral isolation. Recipients were followed up clinically for a period of 6 months after keratoplasty. All recipients but three were found to be HSV seropositive. Eight recipient corneal buttons contained detectable HSV DNA (7 HSV-1, 1 HSV-2, the latter case confirmed by viral culture). Two donor corneas were found positive for HSV-1 DNA, with negative cultures, and endothelial graft failure occurred in one of the matching recipients after 4 months. One recipient with no history of herpes contracted herpetic keratitis 4 months after keratoplasty, even though the corneal button and donor scleral remnants contained no detectable HSV DNA. The study confirms previous observations of HSV DNA in the corneal tissue of HSV seropositive patients apparently unrelated to any clinical manifestation of herpes infection. However, as demonstrated by culture, HSV remains infectious and may therefore induce donor-to-host infection in corneal recipients.

Herpes keratitis in the absence of anterograde transport of virus from sensory ganglia to the cornea

“…As well, HSV could potentially leave the cornea associated with trafficking immune cells and then return at a later time with these cells. Nevertheless, there are numerous observations of HSV either persistent or latent in human corneas (10)(11)(12)(13)(14)(15)(16). Our observations that anterograde spread from ganglia to cornea is not required for disease predict that HSV that remains in the cornea can cause HSK.…”

“…Viral DNA and infectivity are frequently found in human tears and in corneas removed for transplantation (9,(11)(12)(13). Moreover, infectious virus can cause damage to corneas during storage or be transmitted to recipients (9,14,15), and this virus is unlikely to be derived from reactivating neurons, given the time frame of the surgery. Similarly, in rabbits and mice, persistent HSV DNA has also been detected in the corneas long after acute infections have subsided (16,17).…”

Interrelationship of Primary Virus Replication, Level of Latency, and Time to Reactivation in the Trigeminal Ganglia of Latently Infected Mice

“…However, studies from mice indicate that lytic transcripts and proteins are expressed at very low levels in latently infected ganglia (26)(27)(28). There is also human observational data based on tissue sampling, which demonstrated expression of HSV-1 genes during latency (29)(30)(31)(32). Previously we have shown that this low level of HSV-1 gene expression in the presence of LAT is associated with T cell exhaustion in TG of latently infected mice (28).…”

The Role of LAT in Increased CD8 + T Cell Exhaustion in Trigeminal Ganglia of Mice Latently Infected with Herpes Simplex Virus 1

“…However, studies in mice indicate that lytic transcripts and proteins may be expressed at very low levels in latently infected ganglia (15,40). There is also human observational data based on tissue sampling which demonstrated expression of HSV-1 genes during latency (11,28,61,62). Whether this low-level HSV-1 gene expression represents reactivation events or indicates continued low-level viral gene expression during latency remains unclear.…”