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Molecular genetic evidence that the hydrophobic anchors of glycoproteins E2 and E1 interact during assembly of alphaviruses

Strauss, Ellen G. and Lenches, Edith M. and Strauss, James H. (2002) Molecular genetic evidence that the hydrophobic anchors of glycoproteins E2 and E1 interact during assembly of alphaviruses. Journal of Virology, 76 (20). pp. 10188-10194. ISSN 0022-538X. PMCID PMC136572.

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Chimeric alphaviruses in which the 6K and glycoprotein E1 moieties of Sindbis virus are replaced with those of Ross River virus grow very poorly, but upon passage, adapted variants arise that grow >100 times better. We have sequenced the entire domain encoding the E2, 6K, and E1 proteins of a number of these adapted variants and found that most acquired two amino acid changes, which had cumulative effects. In three independent passage series, amino acid 380 of E2, which is in the transmembrane domain, was mutated from the original isoleucine to serine in two instances and to valine once. We have now changed this residue to seven others by site-directed mutagenesis and tested the effects of these mutations on the growth of both the chimera [SIN(RRE1)] and of parental Sindbis. These results indicate that the transmembrane domains of glycoproteins E2 and E1 of alphaviruses interact in a sequence-dependent manner and that this interaction is required for efficient budding and assembly of infectious virions.

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Additional Information:Copyright © 2002, American Society for Microbiology. Received 23 April 2002. Accepted 8 July 2002. We acknowledge Jian-Sheng Yao for helpful discussions and participation during the initial phases of this project. This work was supported by grants AI 10793 and AI 20612 from the National Institutes of Health.
Funding AgencyGrant Number
NIHAI 10793
NIHAI 20612
Issue or Number:20
PubMed Central ID:PMC136572
Record Number:CaltechAUTHORS:STRAjvir02
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:4189
Deposited By: Tony Diaz
Deposited On:06 Aug 2006
Last Modified:02 Oct 2019 23:10

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