Factors that contribute to the transneuronal spread of herpes simplex virus

Abstract

In viral encephalitis and retinal necrosis, different herpes simplex virus (HSV) strains spread between neurons in the central nervous system (CNS) by distinctly different routes. The steps of viral infection and spread in a single neuron type and nearby glial cells in vivo have been determined for three different strains of HSV (F, H129, and McIntyre-B). The corneas of mice were inoculated with equivalent titers of the strains. Two to 5 days later, the animals were killed. The spread of viral proteins within trigeminal cells was examined using immuno- and electron microscopy and Western blots with anti-HSV polyclonal antiserum. McIntyre-B virus infection resulted in fewer labeled ganglion cells, possibly as a result of reduced viral production in the corneal epithelium or trigeminal ganglion cells. Although the McIntyre-B strain was at least as, if not more efficient, at retrograde transport than the other strains, the amount of McIntyre-B virus that was transported in the trigeminal roots in an anterograde direction was significantly less than the other strains. Uptake by ganglionic satellite cells was qualitatively similar for the three strains, but maturation and release of virus from satellite cells to other neurons were reduced in the McIntyre-B strain. These characteristics may account for the preferential retrograde transneuronal spread of McIntyre-B strain.

Ultrastructural Analysis of Virion Formation and Intraaxonal Transport of Herpes Simplex Virus Type 1 in Primary Rat Neurons

“…Thus, there is uncertainty regarding the direction of transport of the observed viral particles. However, contrary to findings in previous studies (21)(22)(23)(31)(32)(33)(34), we observed enveloped HSV-1 virions within vesicles in axons and growth cones, which could not be derived from entry events as could naked capsids during retrograde transport. Thus, the observation itself is of sufficient validity to support the notion that intraaxonal anterograde transport of both PrV and HSV-1 involves enveloped virions within vesicles.…”

“…Besides evidence for separate transport of viral nucleocapsids and envelope components (23,34,37,38), enveloped capsids in vesicles (7,23,27) and sometimes both enveloped and naked nucleocapsids were detected (17,20,36). Recent live-cell imaging studies on transport of fluorescently labeled HSV-1 components provided evidence for cotransport of capsid and envelope components in congruence with the married model (2).…”

Chondrocyte terminal differentiation, apoptosis, and type X collagen expression are downregulated by parathyroid hormone

“…Gene knockout studies have demonstrated that PTHrP and Indian hedgehog (Ihh) repress terminal chondrocyte differentiation in avian and murine models (Lanske et al, , 1999Vortkamp et al, 1996;La Vail et al, 1997;Lanske and Kronenberg, 1998). The data suggest that proliferating chondrocytes express PTHrP receptors and Ihh protein as they begin to differentiate.…”

Satellite glial cells in sensory ganglia: from form to function

“…It appears that in the latent phase the viruses are localized in the neurons of sensory ganglia, but rarely in SGCs [96]. However, SGCs may still have a role in this disease, as they are likely to form a barrier to the spread of the virus between infected and non-infected neurons [91,184]. It can be proposed that a breakdown of this barrier can lead to widespread infection of the ganglia.…”