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Viruses 2013, 5(2), 678-707; doi:10.3390/v5020678

Review

Directional Spread of Alphaherpesviruses in the Nervous System

Tal Kramer ^1,2  and Lynn W. Enquist ^1,*

¹ Princeton University, Department of Molecular Biology, Princeton, NJ 08544, USA ² Children's Hospital Boston and Harvard Medical School, F.M. Kirby Neurobiology Center, Boston, MA 02115, USA

* Author to whom correspondence should be addressed.

Received: 3 January 2013; in revised form: 4 February 2013 / Accepted: 5 February 2013 / Published: 11 February 2013

(This article belongs to the Special Issue Viral Infections of the CNS)

Download PDF Full-Text [755 KB, uploaded 12 February 2013 09:07 CET]

Abstract: Alphaherpesviruses are pathogens that invade the nervous systems of their mammalian hosts. Directional spread of infection in the nervous system is a key component of the viral lifecycle and is critical for the onset of alphaherpesvirus-related diseases. Many alphaherpesvirus infections originate at peripheral sites, such as epithelial tissues, and then enter neurons of the peripheral nervous system (PNS), where lifelong latency is established. Following reactivation from latency and assembly of new viral particles, the infection typically spreads back out towards the periphery. These spread events result in the characteristic lesions (cold sores) commonly associated with herpes simplex virus (HSV) and herpes zoster (shingles) associated with varicella zoster virus (VZV). Occasionally, the infection spreads transsynaptically from the PNS into higher order neurons of the central nervous system (CNS). Spread of infection into the CNS, while rarer in natural hosts, often results in severe consequences, including death. In this review, we discuss the viral and cellular mechanisms that govern directional spread of infection in the nervous system. We focus on the molecular events that mediate long distance directional transport of viral particles in neurons during entry and egress.

Keywords: alphaherpesvirus; herpes simplex virus; pseudorabies virus; axonal transport; directional spread; cytoskeleton

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