Function of Chikungunya Virus Structural Proteins
Chikungunya virus (CHIKV) belongs to the genus Alphavirus (within the family Togaviridae), which includes over 29 species that may cause encephalitis, febrile illness, and arthralgia in humans. CHIKV has a single-stranded, positive sense RNA genome of app
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roduction Chikungunya virus (CHIKV) belongs to the genus Alphavirus (within the family Togaviridae), which includes over 29 species that may cause encephalitis, febrile illness, and arthralgia in humans. CHIKV has a single-stranded, positive sense RNA genome of approximately 12 kb in length, although some size variation exists between different lineages. The icosahedral virions have a diameter of 60–70 nm and consist of a nucleocapsid enveloped by a host-derived phospholipid membrane. The viral structural polyprotein is translated from a ~5 kb subgenomic mRNA and is co- and post-translationally cleaved into capsid protein (C), two major envelope glycoproteins (E1, E2), and three smaller accessory proteins (E3, 6K, and the transframe protein TF). Together, the structural proteins encapsidate the viral genomic RNA to form the viral progeny. The different functions of the individual CHIKV structural proteins in virion assembly, egress, binding, and fusion are reviewed in this chapter.
S.W. Metz Department of Microbiology and Immunology, University of North Carolina, School of Medicine, Chapel Hill, NC, USA Laboratory of Virology, Wageningen University, Droevendaalsesteeg 1, 6708PB, Wageningen, The Netherlands G.P. Pijlman (*) Laboratory of Virology, Wageningen University, Droevendaalsesteeg 1, 6708PB, Wageningen, The Netherlands e-mail: [email protected] © Springer International Publishing Switzerland 2016 C.M. Okeoma (ed.), Chikungunya Virus, DOI 10.1007/978-3-319-42958-8_5
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Chikungunya Virus Capsid Protein The CHIKV nucleocapsid has a T = 4 icosahedral symmetry and consists of the viral RNA encapsidated by 240 capsid protein copies (Fig. 1a, b). The CHIKV capsid protein has a length of 261 amino acids and an apparent molecular weight of ~30 kDa (Khan et al. 2002), which is small enough for passive transport through nuclear pores. The CHIKV capsid protein is organized into 3 regions (I, II, and III) with separate functions (Fig. 1c) (Hong et al. 2006). The capsid protein is autocatalytically cleaved off in cis from the nascent viral structural polyprotein (C-E3-E2-6K-E1) by its C-terminal serine protease which has a chymotrypsin-like fold (Aliperti and Schlesinger 1978; Choi et al. 1991; Melancon and Garoff 1987; Strauss and Strauss 1994). A catalytic serine S213 and several conserved H139, D145, D161 amino acids are predicted to be involved in this autoprotease activity which resides in region III of the capsid coding sequence (Hahn and Strauss 1990; Khan et al. 2002). After the autocatalytic cleavage of the capsid from the structural polyprotein, the signal sequence for ER translocation of PE2 becomes available at the N-terminus. The capsid has a poorly conserved N-terminal region with an alleged role in viral RNA assembly via positively charged Arg, Lys, and Pro residues in region I. Region II is involved in the encapsidation of newly synthesized viral genomic RNA, which is packaged with high specificity due to defined RNA packaging signals within the nsP2 gene. Consequentl
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