The high risk HPV16 L2 minor capsid protein has multiple transport signals that mediate its nucleocytoplasmic traffic

Shahan Mamoor, Zeynep Onder, Balasubramanyam Karanam, Kihyuck Kwak, Jennifer Bordeaux, Lauren Crosby, Richard B.S. Roden, Junona Moroianu

Research output: Contribution to journalArticle

Abstract

In this study we examined the transport signals contributing to HPV16 L2 nucleocytoplasmic traffic using confocal microscopy analysis of enhanced green fluorescent protein-L2 (EGFP-L2) fusions expressed in HeLa cells. We confirmed that both nuclear localization signals (NLSs), the nNLS (1MRHKRSAKRTKR12) and cNLS (456RKRRKR461), previously characterized in vitro (Darshan et al., 2004), function independently in vivo. We discovered that a middle region rich in arginine residues (296SRRTGIRYSRIGNKQTLRTRS316) functions as a nuclear retention sequence (NRS), as mutagenesis of critical arginine residues within this NRS reduced the fraction of L2 in the nucleus despite the presence of both NLSs. Significantly, the infectivity of HPV16 pseudoviruses containing either RR297AA or RR297EE within the L2 NRS was strongly reduced both in HaCaT cells and in a murine challenge model. Experiments using Ratjadone A nuclear export inhibitor and mutation-localization analysis lead to the discovery of a leucine-rich nuclear export signal ( 462LPYFFSDVSL) mediating 16L2 nuclear export. These data indicate that HPV16 L2 nucleocytoplasmic traffic is dependent on multiple functional transport signals.

Original languageEnglish (US)
Pages (from-to)413-424
Number of pages12
JournalVirology
Volume422
Issue number2
DOIs
StatePublished - Jan 20 2012

Keywords

  • Human papillomaviruses
  • L2 minor capsid protein
  • Nuclear export signal
  • Nuclear localization signal
  • Nuclear retention sequence

ASJC Scopus subject areas

  • Virology

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