Alphaherpesvirus axon-to-cell spread involves limited virion transmission

Matthew P. Taylor, Oren Kobiler, Lynn W. Enquist

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)17046-17051
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number42
DOIs
StatePublished - Oct 16 2012

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Cell-cell spread
  • Live-cell imaging

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