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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.

SUBMITTER: Zheng A

PROVIDER: S-EPMC4063126 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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

Zheng Aihua A Yuan Fei F Kleinfelter Lara M LM Kielian Margaret M

Nature communications 20140520

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 p ...[more]

PMID: 24846574

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