Alphaherpesvirus axon-to-cell spread involves limited virion transmission

Department of Molecular Biology, Princeton University, Princeton, NJ 08544.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 10/2012; 109(42):17046-51. DOI: 10.1073/pnas.1212926109
Source: PubMed


The spread of viral infection within a host can be restricted by bottlenecks that limit the size and diversity of the viral population. An essential process for alphaherpesvirus infection is spread from axons of peripheral nervous system neurons to cells in peripheral epithelia (anterograde-directed spread, ADS). ADS is necessary for the formation of vesicular lesions characteristic of reactivated herpesvirus infections; however, the number of virions transmitted is unknown. We have developed two methods to quantitate ADS events using a compartmentalized neuronal culture system. The first method uses HSV-1 and pseudorabies virus recombinants that express one of three different fluorescent proteins. The fluorescence profiles of cells infected with the virus mixtures are used to quantify the number of expressed viral genomes. Strikingly, although epithelial or neuronal cells express 3-10 viral genomes after infection by free virions, epithelial cells infected by HSV-1 or pseudorabies virus following ADS express fewer than two viral genomes. The second method uses live-cell fluorescence microscopy to track individual capsids involved in ADS. We observed that most ADS events involve a single capsid infecting a target epithelial cell. Together, these complementary analyses reveal that ADS events are restricted to small numbers of viral particles, most often a single virion, resulting in a single viral genome initiating infection.

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    • "Another known pathway that viruses utilize to spread within the CNS is axonal transport post-entry into host neurons. Viruses can travel long distances by getting transported across synaptic connections in various sectors of mammalian central and peripheral nervous system (Beier et al., 2011; Taylor et al., 2012). Over the years, HSV and pseudorabies virus (PRV) have been used to visualize axonal transport and the resulting patterns of viral infections in the CNS milieu (Granstedt et al., 2013). "
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