TY - JOUR
T1 - Dealing with low pH
T2 - entry and exit of alphaviruses and flaviviruses
AU - Martín, Claudia Sánchez San
AU - Liu, Catherine Y.
AU - Kielian, Margaret
N1 - Funding Information:
We dedicate this review to the memory of our colleague and friend Dr. Dennis Shields. We thank all of the members of our lab for helpful discussions, and Gwen Taylor, Gleyder Roman-Sosa, Aihua Zheng, Kartik Chandran and Félix Rey for their comments on the manuscript. We also thank Mark Girvin for insightful discussions of amino acid titration. Work in our laboratory was supported by grants to M.K. from the National Institutes of Health (AI075647, AI067931, GM057454, U54AI057158) and by Cancer Center Core Support Grant NIH/NCI P30-CA13330. C.Y.L. was supported in part through the Medical Scientist Training Program of the Albert Einstein College of Medicine (NIH T32 GM07288). We acknowledge the important contributions of those researchers whose work was not fully cited due to space limitations.
PY - 2009/11
Y1 - 2009/11
N2 - The alphaviruses and flaviviruses include many important human pathogens, such as the dengue, West Nile, and Chikungunya viruses. These enveloped viruses infect cells by a membrane fusion reaction triggered by the low pH in endosomes. Fusion is mediated by viral membrane proteins through their acid-dependent conversion from a dimer on the virus surface to a homotrimer inserted into the host cell membrane. Here we review recent studies on the regulatory mechanisms that silence these fusion proteins during virus exit and that sense low pH and mediate protein refolding during virus entry. We discuss results using truncated proteins to dissect the fusion reaction, and future research directions including the development of antiviral therapies against these medically important viruses.
AB - The alphaviruses and flaviviruses include many important human pathogens, such as the dengue, West Nile, and Chikungunya viruses. These enveloped viruses infect cells by a membrane fusion reaction triggered by the low pH in endosomes. Fusion is mediated by viral membrane proteins through their acid-dependent conversion from a dimer on the virus surface to a homotrimer inserted into the host cell membrane. Here we review recent studies on the regulatory mechanisms that silence these fusion proteins during virus exit and that sense low pH and mediate protein refolding during virus entry. We discuss results using truncated proteins to dissect the fusion reaction, and future research directions including the development of antiviral therapies against these medically important viruses.
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U2 - 10.1016/j.tim.2009.08.002
DO - 10.1016/j.tim.2009.08.002
M3 - Review article
C2 - 19796949
AN - SCOPUS:70350340830
SN - 0966-842X
VL - 17
SP - 514
EP - 521
JO - Trends in Microbiology
JF - Trends in Microbiology
IS - 11
ER -
