Alphavirus Entry and Membrane Fusion
Abstract
:1. Introduction
2. Alphavirus architecture and the structure of the fusion machinery
3. The alphavirus entry pathway
3.1. Receptors and attachment factors
3.2. Receptor-mediated endocytosis of alphaviruses
Observation | Selected References | |
---|---|---|
Morphological and biochemical observation of endocytic uptake | [39,43] | |
Infection from within endosomes | [44] | |
Infection/fusion inhibited by dominant-negative inhibitors of endocytosis: | dynamin | [45,46][47][48] |
eps15 | ||
rab-5 | ||
Infection/fusion inhibited by weak bases (e.g. NH4Cl, chloroquine) | [39,44,49] | |
Infection/fusion inhibited by ionophores (e.g. monensin) | [50,51] | |
Infection/fusion inhibited by vacuolar proton pump inhibitors (e.g. bafilomycin, concanamycin) | [46,49,52] | |
Specific low pH-dependence of pseudotype infection | [53] | |
Low pH-dependent cell-cell fusion | [54-57] | |
Low pH-dependent virus fusion with liposomes | [58-60] | |
Low pH-dependent fusion pore formation | [56,61] | |
Mutations block both membrane fusion in vitro and virus infection in vivo | [62-64] | |
Exogenous DIII blocks both fusion and infection | [65] |
3.3. Low pH-triggered fusion in endosomes
4. Alphavirus membrane fusion
4.1. General properties of alphavirus-membrane fusion
4.2. Lipid dependence
4.3. Conformational changes during fusion
Observation | Selected References |
---|---|
Timing during virus uptake in vivo | [51,100] |
In vivo formation requires endosomal acidification | [100] |
Block in homotrimer formation in fusion-defective E1 mutants G91D, D188K | [62,64] |
Timing during virus fusion in vitro | [58,101] |
Correlation with pH-dependence of virus fusion | [35,74] |
Exogenous DIII blocks E1 hairpin formation and fusion | [65] |
4.4. E1 ectodomain studies
4.5. E1 homotrimer structure
4.6. Properties of the alphavirus fusion pore
5. Molecular analysis of the alphavirus membrane fusion reaction
Regulatory role of p62/E2
Virus used for selection | Glycoproteins | References | ||
---|---|---|---|---|
E3 | E2 | E1 | ||
wt/p62 (SFV) | N7D, N77D, A121E, H170Y,L221Q, R244G, R244K, R250G | V11A, T159A | [140,141] | |
SHQL(SFV) | H64R | Q4R, R244I, R244K | [139] | |
TRSB-N(SIN) | C25R | D82G, H169L, P191T, T198M, E216G, N239H | [35,137] | |
VEE deletion | L243N | F253S | [135] | |
SIN E2/RRV 6k+E1(chimera) | D72N, S118N, K131E, I150L, V237F, L243S, D248Y, I380S | S310F, F399S, Q411L, I423L, C433R | [133,142,143] |
E1 fusion loop and target membrane interaction.
Characterization of the E1 homotrimer
Cholesterol dependence
Role of the E1 ij loop
Roles of the E1 stem and transmembrane domains
In vitro reconstitution of trimerization
6. Future directions
Acknowledgments
References
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Kielian, M.; Chanel-Vos, C.; Liao, M. Alphavirus Entry and Membrane Fusion. Viruses 2010, 2, 796-825. https://doi.org/10.3390/v2040796
Kielian M, Chanel-Vos C, Liao M. Alphavirus Entry and Membrane Fusion. Viruses. 2010; 2(4):796-825. https://doi.org/10.3390/v2040796
Chicago/Turabian StyleKielian, Margaret, Chantal Chanel-Vos, and Maofu Liao. 2010. "Alphavirus Entry and Membrane Fusion" Viruses 2, no. 4: 796-825. https://doi.org/10.3390/v2040796