Sorting and Transport of Alpha Herpesviruses in Axons

Tomishima, Mark; Smith, Greg; Enquist, L. W.

doi:10.1034/j.1600-0854.2001.020701.x

Cited by 111 publications

(93 citation statements)

References 56 publications

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“…As with transport in the anterograde direction, spread of ␣-herpesviruses in the retrograde direction, from axon termini to nerve cell bodies, involves axonal microtubule motors that carry capsids to the nucleus, where virus replication occurs (20,21). When HSV enters sensory neurons, viral glycoproteins are deposited in host membranes and capsids move to the nucleus and initiate infection without the glycoproteins (21).…”

Section: Resultsmentioning

confidence: 99%

“…To investigate this source further, we constructed an HSV mutant that replicated normally in the cornea but was unable to return to the cornea from sensory ganglia. Movement of HSV and the related ␣-herpesvirus pseudorabies virus (PRV) from the nerve cell bodies of infected neurons to the periphery apparently involves transport by means of microtubule motors (20,21). There is evidence that nucleocapsids and viral membrane glycoproteins (that make up the virion envelope) move toward axon termini separately, i.e., on different sets of axonal microtubules.…”

mentioning

confidence: 99%

“…A PRV membrane protein, US9, functions to promote movement of viral membrane glycoproteins to axon termini, perhaps by tethering glycoprotein-laden vesicles onto microtubule motors (21). In the absence of US9, PRV glycoproteins remain in neuron cell bodies, and no infectious progeny are produced at axon tips (21,22). HSV expresses a homolog of PRV US9 (23).…”

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confidence: 99%

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Herpes keratitis in the absence of anterograde transport of virus from sensory ganglia to the cornea

Polcicova

Biswas

Banerjee

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Herpes stromal keratitis is an immunopathologic disease in the corneal stroma leading to scarring, opacity, and blindness, and it is an important problem in common corneal surgeries. Paradoxically, virus antigens are largely focused in the epithelial layer of the cornea and not in the stromal layer, and viral antigens are eliminated before stromal inflammation develops. It is not clear what drives inflammation, whether viral antigens are necessary, or how viral antigens reach the stroma. It has been proposed that herpes simplex virus (HSV) travels from the corneal epithelium to sensory ganglia then returns to the stroma to cause disease. However, there is also evidence of HSV DNA and infectious virus persistent in corneas, and HSV can be transmitted to transplant recipients. To determine whether HSV resident in the cornea could cause herpes stromal keratitis, we constructed an HSV US9 ؊ mutant that had diminished capacity to move in neuronal axons. US9 ؊ HSV replicated and spread normally in the mouse corneal epithelium and to the trigeminal ganglia. However, US9 ؊ HSV was unable to return from ganglia to the cornea and failed to cause periocular skin disease, which requires zosteriform spread from neurons. Nevertheless, US9 ؊ HSV caused keratitis. Therefore, herpes keratitis can occur without anterograde transport from ganglia to the cornea, probably mediated by virus persistent in the cornea. ocular infection ͉ stroma ͉ neurons ͉ US9 cell-to-cell spread ͉ persistent herpes simplex virus

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Herpes keratitis in the absence of anterograde transport of virus from sensory ganglia to the cornea

Polcicova

Biswas

Banerjee

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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“…The relative contribution of other tegument or capsid proteins to HSV-1 transport is not known, although it has been suggested that the major tegument protein pUL36, or one of the minor capsid proteins such as pUL25, may also contribute to dynein binding in vivo [51,67]. In the case of PrV, the so-called inner tegument proteins pUL36, pUL37 and pUS3 have been shown to remain associated with the capsid during entry HSV transport and egress HSV transport and egress 39 39 [68,69].…”

Section: Dynein Cofactor: Dynactinmentioning

confidence: 99%

Transport and egress of herpes simplex virus in neurons

Diefenbach

Miranda-Saksena

Douglas

et al. 2007

Reviews in Medical Virology

166

150

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The mechanisms of axonal transport of the alphaherpesviruses, HSV and pseudorabies virus (PrV), in neuronal axons are of fundamental interest, particularly in comparison with other viruses, and offer potential sites for antiviral intervention or development of gene therapy vectors. These herpesviruses are transported rapidly along microtubules (MTs) in the retrograde direction from the axon terminus to the dorsal root ganglion and then anterogradely in the opposite direction. Retrograde transport follows fusion and deenvelopment of the viral capsid at the axonal membrane followed by loss of most of the tegument proteins and then binding of the capsid via one or more viral proteins (VPs) to the retrograde molecular motor dynein. The HSV capsid protein pUL35 has been shown to bind to the dynein light chain Tctex1 but is likely to be accompanied by additional dynein binding of an inner tegument protein. The mechanism of anterograde transport is much more controversial with different processes being claimed for PrV and HSV: separate transport of HSV capsid/tegument and glycoproteins versus PrV transport as an enveloped virion. The controversy has not been resolved despite application, in several laboratories, of confocal microscopy (CFM), realtime fluorescence with viruses dual labelled on capsid and glycoprotein, electron microscopy in situ and immunoelectron microscopy. Different processes for each virus seem counterintuitive although they are the most divergent in the alphaherpesvirus subfamily. Current hypotheses suggest that unenveloped HSV capsids complete assembly in the axonal growth cones and varicosities, whereas with PrV unenveloped capsids are only found travelling in a retrograde direction.

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“…Although the molecular basis is not completely understood, members of the Herpesviridae family are examples of agents using this transport system [50] as well as neurotoxins (i.e. tetanus toxin, [41]).…”

Section: Discussionmentioning

confidence: 99%

Propagation of scrapie in peripheral nerves after footpad infection in normal and neurotoxin exposed hamsters

et al. 2007

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-As is known from various animal models, the spread of agents causing transmissible spongiform encephalopathies (TSE) after peripheral infection affects peripheral nerves before reaching the central nervous system (CNS) and leading to a fatal end of the disease. The lack of therapeutic approaches for TSE is partially due to the limited amount of information available on the involvement of host biological compartments and processes in the propagation of the infectious agent. The in vivo model presented here can provide information on the spread of the scrapie agent via the peripheral nerves of hamsters under normal and altered axonal conditions. Syrian hamsters were unilaterally footpad (f.p.) infected with scrapie. The results of the spatiotemporal ultrasensitive immunoblot-detection of scrapie-associated prion protein (PrP Sc ) in serial nerve segments of both distal sciatic nerves could be interpreted as a centripetal and subsequent centrifugal neural spread of PrP Sc for this route of infection. In order to determine whether this propagation is dependent on main components in the axonal cytoskeleton (e.g. neurofilaments, also relevant for the component 'a' of slow axonal transport mechanisms), hamsters were treated -in an additional experiment-with the neurotoxin ß,ß'-iminodiproprionitrile (IDPN) around the beginning of the scrapie infection. A comparison of the Western blot signals of PrP Sc in the ipsilateral and in the subsequently affected contralateral sciatic nerve segments with the results revealed from IDPN-untreated animals at preclinical and clinical stages of the TSE disease, indicated similar amounts of PrP Sc . Furthermore, the mean survival time was unchanged in both groups. This in vivo model, therefore, suggests that the propagation of PrP Sc along peripheral nerves is not dependent on an intact neurofilament component of the axonal cytoskeleton. Additionally, the model indicates that the spread of PrP Sc is not mediated by the slow component 'a' of the axonal transport mechanism.scrapie / PrP Sc / nerve / footpad / IDPN

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Sorting and Transport of Alpha Herpesviruses in Axons

Cited by 111 publications

References 56 publications

Herpes keratitis in the absence of anterograde transport of virus from sensory ganglia to the cornea

Herpes keratitis in the absence of anterograde transport of virus from sensory ganglia to the cornea

Transport and egress of herpes simplex virus in neurons

Propagation of scrapie in peripheral nerves after footpad infection in normal and neurotoxin exposed hamsters

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