Uptake and Transport of Herpes Simplex Virus in Neurites of Rat Dorsal Root Ganglia Cells in Culture

Lycke, Erik; Kristensson, Krister; Svennerholm, Bo; Vahlne, Anders; Ziegler, Richard J.

doi:10.1099/0022-1317-65-1-55

Cited by 127 publications

(102 citation statements)

References 18 publications

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“…Within neurons, HSV-1 nucleocapsid and tegument proteins travel in a retrograde manner to the neuronal cell body where the viral genome is released into the nucleus. [96][97][98] The transport of alphaherpesvirus nucleocapsids along axons has been estimated to occur at rates of 0.5-3.5 mm/s, 99 suggesting that transport is an active process. While the exact mechanism of HSV transport along axons has yet to be elucidated, recent studies have identified viral and host cell components that contribute to this process.…”

Section: Virus Attachment and Entrymentioning

confidence: 99%

HSV trafficking and development of gene therapy vectors with applications in the nervous system

et al. 2005

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Herpes simplex virus type 1 (HSV-1) is a neurotropic doublestranded DNA virus that causes cold sores, keratitis, and rarely encephalitis in humans. Nonpathogenic HSV-1 gene transfer vectors have been generated by elimination of viral functions necessary for replication. The life cycle of the native virus includes replication in epithelial cells at the site of initial inoculation followed by retrograde axonal transport to the nuclei of sensory neurons innervating the area of cutaneous primary infection. In this review, we summarize the current understanding of the molecular basis for HSV cell entry, nuclear transport of the genome, virion egress following replication, and retrograde and anterograde axonal transport in neurons. We discuss how each of these properties has been exploited or modified to allow the generation of gene transfer vectors with particular utility for neurological applications. Recent advances in engineering virus entry have provided proof of principle that vector targeting is possible. Furthermore, significant and potentially therapeutic modifications to the pathological responses to various noxious insults have been demonstrated in models of peripheral nerve disease. These applications exploit the natural axonal transport mechanism of HSV, allowing transgene expression in the cell nucleus within the inaccessible trigeminal ganglion or dorsal root ganglion, following the noninvasive procedure of subcutaneous vector inoculation. These findings demonstrate the importance of understanding basic virology in the design of vector systems and the powerful approach of exploiting favorable properties of the parent virus in the generation of gene transfer vectors. Gene Therapy (2005) 12, 891-901.

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Section: Virus Attachment and Entrymentioning

confidence: 99%

HSV trafficking and development of gene therapy vectors with applications in the nervous system

et al. 2005

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“…HSV is thought to travel retrogradely toward the cell nucleus in the absence of a viral envelope or a cell-derived membrane compartment (Lycke et al, 1984(Lycke et al, , 1988Marchand and Schwab, 1986). Although HSV has not yet been evaluated in in vitro mobility assays, these data suggest that the virus is transported on axonal microtubules in a manner similar to the translocation of fluorescent microspheres, microinjected beads, paraffin droplets, or glass fragments (Adams and Bray, 1983;Colin et al, 1989).…”

Section: Autoradrographymentioning

confidence: 99%

Microtubule polarity in the peripheral processes of trigeminal ganglion cells: relevance for the retrograde transport of herpes simplex virus

1994

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The directional movement of many cellular organelles in neurons is dependent on polarized microtubules and direction-specific motor molecules. Microtubules are also thought to mediate the retrograde transport of herpes simplex virus (HSV) in sensory neurons. To define the cellular machinery responsible for retrograde axonal transport of HSV, we have investigated the polarity of microtubules in the peripheral axons of trigeminal ganglion neurons. The long ciliary nerves of rabbits were prepared for a standard “hook assay” of microtubule polarity. Axons in cross-sectioned nerves contained microtubules with almost uniform orientation. The fast-growing, plus ends of these axonal microtubules are located distal to the cell body and the slow-growing, minus ends are directed centrally. To determine the role played by microtubules in the retrograde transport of HSV in these axons, we injected the retrobulbar space of mice with the microtubule-inhibiting drugs colchicine, vinblastine, or nocodazole or with the microfilament inhibitor cytochalasin D and 1 d later inoculated the cornea with HSV. We found that colchicine, vinblastine, or nocodazole reduced by 52–87% the amount of virus recovered from the ganglion 3 d postinoculation, compared to vehicle-treated animals. In contrast, cytochalasin D or beta-lumicolchicine did not significantly reduce the amount of HSV recovered from the ganglion. We conclude that the retrograde axonal transport of HSV from axon endings in the cornea to the trigeminal ganglion cell bodies requires intact microtubules and occurs in a plus-to-minus direction on the microtubules. Our data are consistent with the hypothesis that the retrograde axonal transport of HSV is mediated by a minus end-directed motor molecule, for example, cytoplasmic dynein.

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“…DRG ceils were obtained by dissecting 10 to 12 Wistar rat embryos (at day 15 to 17) as described in earlier reports (Lycke et al, 1984;Lycke & Tsiang, 1987). Ganglia were collected using forceps under a dissection microscope and cells were dissociated by treatment with 0.25 % trypsin in Ca 2+-and Mg2+-free Hanks' buffer at pH 7.2 for 30 min at 37 °C.…”

Section: Virusmentioning

confidence: 99%

“…Whereas conventional neuronal cultures are less appropriate for the investigation of viral transport, neurons cultivated in a compartmentalized culture system as described by Campenot (1977) will demonstrate convincingly the transport of herpes simplex virus in vitro (Kristensson et al, 1986;Lycke et al, 1984;Ziegler & Herman, 1980) and the retrograde transport of both fixed and street rabies viruses in cultured rat sensory neurons (Lycke & Tsiang, 1987;Tsiang, 1988). In this system, herpes and rabies viruses were transported in a retrograde fashion with a velocity in the range of 50 mm/day (herpes virus) and 25 mm/day (rabies virus) (Lycke et al, 1984;Lycke & Tsiang, 1987).…”

Section: Introductionmentioning

confidence: 99%

The Anterograde Transport of Rabies Virus in Rat Sensory Dorsal Root Ganglia Neurons

Tsiang¹,

Lycke²,

Ceccaldi³

et al. 1989

Journal of General Virology

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SUMMARYWe have previously described the capacity of neurites extending from cultured rat sensory dorsal root ganglia (DRG) neurons to transport rabies virus through axoplasm in the retrograde direction. Here we report the infection of cultured neurons derived from the DRG and the subsequent anterograde transport of rabies virus from the infected cell somas through the extending neurites to its release into the culture supernatant. Viral transport was monitored by titration of the virus yield in the external compartment. Both early and late transport mechanisms of rabies virions were identified. The first one occurred a few hours post-infection and was undetectable 6 h later, before the initiation of viral replication. The velocity of this first wave of infective virions was in the range of 100 to 400 mm/day. The early viral transport was probably the result of a direct translocation of infective virions from the somatic site of entry to the neuritic extensions and subsequent release into the culture medium without replication in the cellular perikaryon. The second virus transport peak was detected 48 h post-infection. In this case, the virions detected in the neuritic compartment were presumably the progeny of the inoculated virus which had replicated in the perikaryon before the viral transport occurs. Using a four-compartment culture device we were able to demonstrate, simultaneously, retrograde and anterograde transport of the virus. The presence of antirabies serum in contact with the exposed neurites did not inhibit either the retrograde or the anterograde transport mechanisms. The viral release from the neuritic extensions after the fast anterograde transport was evaluated to be in the range of 150 to 300 infectious virions per bundle of neurites per day.

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Uptake and Transport of Herpes Simplex Virus in Neurites of Rat Dorsal Root Ganglia Cells in Culture

Cited by 127 publications

References 18 publications

HSV trafficking and development of gene therapy vectors with applications in the nervous system

HSV trafficking and development of gene therapy vectors with applications in the nervous system

Microtubule polarity in the peripheral processes of trigeminal ganglion cells: relevance for the retrograde transport of herpes simplex virus

The Anterograde Transport of Rabies Virus in Rat Sensory Dorsal Root Ganglia Neurons

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