Abstract
Purpose :
AIDS patients are susceptible to a variant of acute retinal necrosis (ARN) termed progressive outer retinal necrosis (PORN) of varicella-zoster virus or HSV1 origin. We used mice with retrovirus-induced immunosuppression (MAIDS) to develop a new mouse model to investigate the pathogenesis of AIDS-related PORN following intraocular HSV1 infection. Although animals developed a retinal disease reminiscent of AIDS-related PORN, they failed to develop acute herpes simplex encephalitis (HSE) as expected. We therefore performed studies to determine if MAIDS mice with HSV1 PORN subsequently develop subclinical HSE.
Methods :
The right eyes of groups of mice with MAIDS were infected intraocularly with 104 PFU of different strains of HSV1 including KOS-63, KOS-79, and H299, the latter virus strain isolated from the eye of an otherwise healthy patient with ARN and with MRI findings consistent with subclinical HSE. HSV1-infected whole eyes and right brain halves were collected at 3, 5, 7, and 10 days postinfection from all animals and subjected to plaque assay for quantification of infectious virus. Parallel animal groups were treated with liposomal clodronate or liposomal vehicle (control) for macrophage depletion. Whole spleens were collected and subjected to flow cytometric analysis for determination of percent macrophage depletion.
Results :
Whereas whole eyes of KOS-63, KOS-79, or H299-infected mice with MAIDS all developed PORN-like retinal disease accompanied by high amounts of infectious virus (103 to 104 PFU/eye) at all times examined, right brain halves of all animals consistently showed no detectable infectious virus or exceedingly low amounts of infectious virus (<20 PFU/brain half) at all times examined and without development of acute HSE by 10 days postinfection. Macrophage depletion (>80%) did not alter these results.
Conclusions :
Three distinct HSV1 strains indeed travel from retina to brain in mice with MAIDS-related HSV1 PORN, but virus infection is found within brain parenchyma at such exceedingly low levels that acute HSE does not develop. Instead, low amounts of infectious HSV1 result in subclinical HSE during MAIDS. Macrophages of innate immunity do not play a role in containing virus spread. Present studies are focused on antiviral interferons. We describe a new mouse model to investigate AIDS-related subclinical HSE.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.