Selective spread of herpes simplex virus through the central nervous system in a murine model of the acute retinal necrosis syndrome

Date of Award




Degree Name

Doctor of Philosophy (Ph.D.)

First Committee Member

Sally S. Atherton - Committee Chair


The acute retinal necrosis (ARN) syndrome is a rare human disorder with a unique clinical presentation characterized by a severe unilateral or bilateral vaso-occlusive retinitis. Most patients with ARN become blind in affected eyes either as a direct result of acute inflammation or from subsequent retinal detachments. ARN usually occurs in immunocompetent individuals who are otherwise healthy, but several cases of ARN in patients with the acquired immunodeficiency syndrome (AIDS) have been reported. Several members of the herpesvirus family are implicated as causative agents in ARN, including herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), varicella zoster virus (VZV), and cytomegalovirus (CMV). Although previous studies have shown that ARN may be associated with spread of virus through the central nervous system (CNS), the precise route by which virus reaches the retina in humans is unknown. We hypothesized that in humans with ARN, virus may spread from one or more foci of infection within the brain along specific neuroanatomical pathways to the retina. To evaluate this hypothesis we studied the spread of virus through the nervous system in an experimental murine model of HSV-1 induced ARN. We have identified several neuroanatomical pathways which allow virus to spread to one or both retinas after transport through the CNS in mice. Our results demonstrate a correlation between the spread of virus along specific neural pathways and the pattern of retinal pathology produced in mice. Several factors influence the spread of HSV-1 along these neural pathways, including the neuroinvasive properties of the virus strain and the immune status of the host. In immunocompetent euthymic BALB/c mice, the spread of neuroinvasive and nonneuroinvasive strains of HSV-1 through the CNS differed in the timing and distribution of virus infection. Our findings suggest that a T cell-dependent immune response may interfere with the spread of nonneuroinvasive strains of HSV-1 through the CNS, but that the immune response has little or no effect on the spread of neuroinvasive viruses in mice.


Biology, Microbiology; Health Sciences, Pathology

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