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

Virology 2012 Jan 6;422(2):413-24. Epub 2011 Dec 6.

Biology Department, Boston College, Chestnut Hill, MA 02467, USA.

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 ((462)LPYFFSDVSL) mediating 16L2 nuclear export. These data indicate that HPV16 L2 nucleocytoplasmic traffic is dependent on multiple functional transport signals.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.virol.2011.11.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249505PMC
January 2012

Publication Analysis

Top Keywords

nuclear export
12
transport signals
12
nucleocytoplasmic traffic
12
hpv16 nucleocytoplasmic
8
nrs reduced
8
arginine residues
8
nuclear
5
mutagenesis critical
4
nrs mutagenesis
4
sequence nrs
4
residues nrs
4
despite presence
4
presence nlss
4
nlss infectivity
4
nucleus despite
4
fraction nucleus
4
retention sequence
4
reduced fraction
4
critical arginine
4
296srrtgirysrignkqtlrtrs316 functions
4

Similar Publications