Anterograde, transneuronal transport of herpes simplex virus type 1 strain H129 in the murine visual system

Abstract

Herpes simplex virus (HSV) undergoes retrograde and anterograde axonal transport as it establishes latency and later intermittently reactivates. Most strains of HSV show preferential retrograde transport within the central nervous system (CNS), however. Previous experiments suggest that an exception to this is HSV type 1 (HSV-1) strain H129, since this virus appears to spread primarily in the CNS via anterograde, transneuronal movement. The objective of the present study was to test how specifically this virus spreads in the visual system, a system with well-described neuronal connections. In the present study, the pattern of viral spread was examined following inoculation into the murine vitreous body. Virus was initially detected in the retina and optic tract. Virus then appeared in all known primary targets of the retina, including those in the thalamus (e.g., lateral geniculate complex), hypothalamus (suprachiasmatic nucleus), and superior colliculus (superficial layers). In previous studies, many strains of HSV were shown to infect these structures, even though they spread predominantly in a retrograde direction. However, the H129 strain was unique in then spreading, via anterograde transport, to the primary visual cortex (layer 4 of area 17) via thalamocortical connections. At later times after infection, specific labeling was also detected in other cortical and subcortical areas known to receive projections from the visual cortex. No labeling was ever detected in the contralateral retina, which is consistent with a lack of retrograde spread of HSV-1 strain H129. These results demonstrate the specific anterograde movement of this virus from the retina to subcortical and cortical regions, with no clear evidence for retrograde spread. HSV-1 strain H129 should be generally useful for tracing sensory pathways and may provide the basis for designing a virus vector capable of delivering genetic material via anterograde pathways within the CNS.