Abstract
PURPOSE: To document the presence of herpes simplex virus (HSV) genomic signatures among Acanthamoeba hosts recovered from patients with Acanthamoeba keratitis (AK) and in contaminated lens cases. METHODS: We used a combination of PCR sequencing and shotgun metagenomics to detect and confirm the presence of HSV genomic signatures in Acanthamoeba hosts and lens cases. Clinical outcomes were correlated with the prevalence of host HSV signatures. RESULTS: HSV genomic signatures were detected in 26% (n = 6) of Acanthamoeba hosts recovered from patients with culture confirmed AK. HSV-1 and HSV-2 or both were identified in 33%, 50%, and 17% of isolates, respectively. Fifty-two percent of patients (12/23) were misdiagnosed initially as presenting with HSV keratitis. Patients with HSV-positive Acanthamoeba isolates had a mean best-corrected visual acuity of 1.43 LogMAR at diagnosis and 0.53 LogMAR at follow-up, compared with 1.85 and 0.92 LogMAR, respectively, in HSV-negative cases. Contact lens use was identified as a risk factor in 83% of 18 patients. We detected 46,597 viral signatures in 5 of 14 contaminated lens cases (35.7%). Distribution included 33% bacteriophages, 8.2% giant viruses, 4.1% nonhuman Herpesviridae, and 0.39% human Herpesviridae. Among the 184 human Herpesviridae genomic signatures, HSV types 1 or 2 or both were documented in 5.7%, VZV in 39.7%, HHV7 in 38.6%, HHV6 in 15.0%, and Epstein-Barr virus in 0.5%. CONCLUSIONS: This study is the first to identify HSV-positive genomic signatures in clinical AK isolates and/or contact lens cases. Taken together, the high prevalence of HSV genomic signatures in both amebic hosts and lens cases, might signal an unrecognized Acanthamoeba-HSV association and the need for reassessing current management.