A Model of In Vivo HSV-1 DNA Transport Using Murine Retinal Ganglion Cells.

Mammalian nervous tissues are heterogeneous. The retina, brain, spinal cord, and peripheral sensory and autonomic ganglia are each composed of neuronal and glial cell partners embedded in a connective tissue bed and supplied by vascular and immune cells. This complicated structure presents many challenges to neuroscientists and cell biologists (e.

The Basic Domain of Herpes Simplex Virus 1 pUS9 Recruits Kinesin-1 To Facilitate Egress from Neurons.

Unlabelled: The alphaherpesviral envelope protein pUS9 has been shown to play a role in the anterograde axonal transport of herpes simplex virus 1 (HSV-1), yet the molecular mechanism is unknown. To address this, we used an in vitro pulldown assay to define a series of five arginine residues within the conserved pUS9 basic domain that were essential for binding the molecular motor kinesin-1. The mutation of these pUS9 arginine residues to asparagine blocked the binding of both recombinant and native kinesin-1.

In vivo HSV-1 DNA transport studies using murine retinal ganglion cells.

The mammalian retina, brain, spinal cord, and peripheral ganglia are all heterogeneous tissues. Each is composed of neuronal and glial cell partners embedded in a connective tissue bed and supplied by vascular and immune cells. This complicated structure presents many challenges to neuroscientists and cell biologists, e.

Delivery of herpes simplex virus to retinal ganglion cell axon is dependent on viral protein Us9.

Purpose: How herpes simplex virus (HSV) is transported from the infected neuron cell body to the axon terminal is poorly understood. Several viral proteins are candidates for regulating the process, but the evidence is controversial. We compared the results of Us9 deletions in two HSV strains (F and NS) using a novel quantitative assay to test the hypothesis that the viral protein Us9 regulates the delivery of viral DNA to the distal axon of retinal ganglion cells in vivo.

Characterization of a UL49-null mutant: VP22 of herpes simplex virus type 1 facilitates viral spread in cultured cells and the mouse cornea.

Herpes simplex virus type 1 (HSV-1) virions, like those of all herpesviruses, contain a proteinaceous layer termed the tegument that lies between the nucleocapsid and viral envelope. The HSV-1 tegument is composed of at least 20 different viral proteins of various stoichiometries. VP22, the product of the U(L)49 gene, is one of the most abundant tegument proteins and is conserved among the alphaherpesviruses.

Genetic and molecular in vivo analysis of herpes simplex virus assembly in murine visual system neurons.

Herpes simplex virus (HSV) infects both epithelial cells and neuronal cells of the human host. Although HSV assembly has been studied extensively for cultured epithelial and neuronal cells, cultured neurons are biochemically, physiologically, and anatomically significantly different than mature neurons in vivo. Therefore, it is imperative that viral maturation and assembly be studied in vivo.

Temporal expression of herpes simplex virus type 1 mRNA in murine retina.

Purpose: During maturation of herpes simplex virus type 1 (HSV) in infected murine retinal F strain ganglion cells, new viral components are axonally transported in two phases. The viral envelope protein (gD) appears 48 hr before the capsid protein (VP5). Our hypothesis was that delayed appearance of VP5 mRNA in the infected eye causes the delayed expression of the VP5 protein in the axon.

A procedure to deliver herpes simplex virus to the murine trigeminal ganglion.

Although initial herpes simplex virus (HSV) infections of the cornea are relatively easily treated, recurrent infections following reactivation of latent virus in the sensory ganglion cells are more difficult to treat. Untreated infections may result in severe consequences, including corneal scarring, glaucoma, and encephalitis. To develop such treatments, an experimental in vivo model was needed in which HSV can be applied directly to trigeminal ganglion cells.

Axonal transport and sorting of herpes simplex virus components in a mature mouse visual system.

The time course for delivery and transport of two major proteins of herpes simplex virus (HSV) has been determined for mature mouse retinal ganglion cell axons in vivo. Twenty-four hours after intravitreal injection of HSV, valacyclovir was introduced into the drinking water of the mice to inhibit subsequent viral replication. Without treatment, viral spread and replication in periaxonal glial cells confound study of axonal transport.