Restriction Factors and Chikungunya Virus
The increasing prevalence of chikungunya virus (CHIKV) in the United States and around the world, and the lack of antiviral treatments or vaccines highlight the potential threat of a global CHIKV pandemic. CHIKV is a mosquito-borne alphavirus that is curr
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roduction Host-encoded viral restriction factors are part of the cell-intrinsic defenses of the innate immune system, also called intrinsic immunity. Contrary to other cell-based antiviral responses that require de novo gene activation, expression, and protein translation, restriction factors are constitutively expressed in most cell types and they act to prevent the infection and spread of viruses. To be classified as a restriction factor, a protein has to meet four criteria including, (1) the ability to restrict virus replication, (2) susceptibility to neutralization by viral encoded factor(s), (3) the presence of signatures of positive selection, and (4) the ability to respond to interferon (IFN) signaling (Harris et al. 2012). Thus far, a handful of restriction factors have been discovered to impede retroviral infection. These include apolipoprotein B mRNA editing enzyme, catalytic polypeptide 3 (APOBEC3), bone marrow stromal antigen 2 (BST-2/tetherin), MX dynamin-like GTPase 2 (MxB), SAM domain and HD domain 1 (SAMHD1), Schlafen 11 (SLFN11), and Tripartite motif protein 5α (TRIM-5α). Of these, only BST-2/tetherin has been implicated in CHIKV pathogenesis at the time of this report. Here, we discuss available data on BST-2-mediated restriction of CHIKV infection of host cells and the release of nascent CHIKV particles from host cells. Also discussed is the regulation of BST-2 by CHIKV. BST-2 is an IFN-inducible type II transmembrane protein (Ishikawa et al. 1995) mainly located on the cell membrane but also present in intracellular compartments, such as the endoplasmic reticulum (ER), trans-Golgi apparatus (TGN), and early endosomes (Hotter et al. 2013; Hammonds et al. 2012; Habermann et al. 2010; Fujita et al. 2012). W.D. Mahauad-Fernandez • C.M. Okeoma (*) Department of Microbiology, University of Iowa, Iowa City, IA, USA Interdisciplinary Program in Molecular and Cellular Biology, University of Iowa, Iowa City, IA, USA e-mail: [email protected] © Springer International Publishing Switzerland 2016 C.M. Okeoma (ed.), Chikungunya Virus, DOI 10.1007/978-3-319-42958-8_11
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Fig. 1 BST-2 structure and isoforms. (a) BST-2 is a type II transmembrane protein with a cytoplasmic tail at the N-terminus followed by a transmembrane domain (TM), an extracellular coiledcoil ectodomain (ECD) and a glycosylphosphatidylinositol (GPI) anchor on the C-terminus embedded in lipid rafts in the plasma membrane. Numbers in red correspond to specific amino acids on the extracellular domain. Amino acids 53, 63, and 91 correspond to cysteines involved in BST-2 homodimerization through disulfide bonds. Amino acids 65 and 92 correspond to asparagines that are glycosylated, an important post-translational modification involved in BST-2 intracellular trafficking. (b) Box depiction of the BST-2 protein. Letters correspond to amino acids that make the cytoplasmic tail (left) and a section of the extracellular domain (right). On top is the sequence for the long isoform of BST-2 (L-BST-2) wh
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