Figure 1.

CHIKV replication cycle. Upon receptor binding, the virus particle is endocytosed. Within the endosome, the pH lowers, triggering the fusion of the viral envelope and endosomal membrane. This releases the nucleocapsid into the cytoplasm which disassembles, liberating the viral genome. Once the genome is in the cytoplasm, viral nonstructural proteins (nsP1–4) are translated (using the host's translation machinery) and complex to form the viral replicase. The viral replicase then synthesizes a negative-sense RNA strand from the positive-sense genome template. The negative-sense RNA serves as a template for the generation of two things: the full-length positive-sense genome (which becomes packaged into the new viral particles) and the subgenomic (26S) RNA, which enables the expression of the structural polyprotein (C-E3-E2-6K-E1). Further processing cleaves the structural polyprotein into the individual structural proteins, including the capsid, which assembles together with the genome to form the nucleocapsid. As the nucleocapsid buds out through the plasma membrane it acquires a portion of the host plasma membrane with embedded viral glycoproteins that will form the envelope of the viral particle. Abbreviations: nsP, non-structural protein; ER, endoplasmic reticulum; pE2, precursor of E2.