The cytoplasmic tails of Uukuniemi virus (Bunyaviridae) GN and GC glycoproteins are important for intracellular targeting and the budding of virus-like particles

Anna K. Överby, Vsevolod L. Popov, Ralf F. Pettersson, Etienne P.A. Neve

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Functional motifs within the cytoplasmic tails of the two glycoproteins GN and GC of Uukuniemi virus (UUK) (Bunyaviridae family) were identified with the help of our recently developed virus-like particle (VLP) system for UUK virus (A. K. Overby, V. Popov, E. P. Neve, and R. F. Pettersson, J. Virol. 80:10428-10435, 2006). We previously reported that information necessary for the packaging of ribonucleoproteins into VLPs is located within the GN cytoplasmic tail (A. K. Overby, R. F. Pettersson, and E. P. Neve, J. Virol. 81:3198-3205, 2007). The GN glycoprotein cytoplasmic tail specifically interacts with the ribonucleoproteins and is critical for genome packaging. In addition, two other regions in the GN cytoplasmic tail, encompassing residues 21 to 25 and 46 to 50, were shown to be important for particle generation and release. By the introduction of point mutations within these two regions, we demonstrate that leucines at positions 23 and 24 are crucial for the initiation of VLP budding, while leucine 46, glutamate 47, and leucine 50 are important for efficient exit from the endoplasmic reticulum and subsequent transport to the Golgi complex. We found that budding and particle generation are highly dependent on the intracellular localization of both glycoproteins. The short cytoplasmic tail of UUK GC contains a lysine at position -3 from the C terminus that is highly conserved among members of the Phlebovirus, Hantavirus, and Orthobunyavirus genera. Mutating this single amino acid residue in GC resulted in the mislocalization of not only GC but also G N to the plasma membrane, and VLP generation was compromised in cells expressing this mutant. Together, these results demonstrate that the cytoplasmic tails of both GN and GC contain specific information necessary for efficient virus particle generation.

Original languageEnglish (US)
Pages (from-to)11381-11391
Number of pages11
JournalJournal of virology
Volume81
Issue number20
DOIs
StatePublished - Oct 2007

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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