Alphavirus Replication: The Role of Cardiac Glycosides and Ion Concentration in Host Cells

Figure 1

The role of ion concentration during alphavirus replication. Alphavirus infection is initiated by attachment (a-i) and binding to the host cell surface receptor and the virus is then internalized by endocytosis (a-ii). During virus fusion with the host cell membrane (a-iii), a high H⁺ concentration inside the endosome promotes degradation of the capsid protein, nucleocapsid disassembly (b-iv), and release of the viral genome into the cytoplasm (b-v). The genomic RNA is the template for protein translation from both whole genomic and subgenomic (26S) RNA (c-vi) and also the transcription of RNA (+) via a RNA (−) template intermediary (c-vii). The viral genome is replicated (c-iii) and incorporated into a new viral particle. The last phase is the virus budding at the host cell membrane in the presence of elevated H⁺ ion concentration (d-ix) followed by virion release (d-x). The inhibition of Na⁺ K⁺ ATPase by the cardiac glycoside, ouabain (OUA) (a-xi), results in a change cell osmotic concentration and (c-vi) interrupting synthesis polyprotein through ion change and/or by cell signaling pathways that limit virus replication.

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