A toggle switch controls the low pH-triggered rearrangement and maturation of the dengue virus envelope proteins.

Abstract

Immature dengue virus particles undergo a dramatic conformational change upon exposure to the acidic environment of the late secretory pathway. The interactions of the E fusion proteins and prM chaperone proteins on the virus envelope are reorganized to permit prM processing by a host protease, furin, thus priming virus for fusion and infection. Here we identify a pH-dependent toggle switch that controls this key conformational change during virus maturation. Our data show that the M region of prM interacts with E at neutral pH but is released at acidic pH, while the pr region interacts with E at acidic pH but is released at neutral pH. Alanine substitution of the conserved residue H98 in prM disrupts the switch by inhibiting dissociation of M from E at low pH, resulting in impaired prM processing and decreased virus infectivity. Thus, release of M-E interaction at low pH promotes formation of a furin-accessible intermediate.

• Authors: Aihua Zheng, Fei Yuan, Lara M Kleinfelter, Margaret Kielian
• Journal: Nature communications (Nat Commun) Vol. 5 Pg. 3877 (May 20 2014) ISSN: 2041-1723 [Electronic] England
• PMID: 24846574 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Viral Envelope Proteins
• Furin

Topics

• Dengue Virus (metabolism)
• Furin (metabolism)
• Humans
• Hydrogen-Ion Concentration
• Viral Envelope Proteins (metabolism)