Hepatitis C virus: viral proteins on the move

Abstract

There is now increasing evidence that LDs (lipid droplets) play a central role in the production of infectious HCV (hepatitis C virus) and participate in virus assembly. Two viral proteins, namely core, which forms the capsid, and NS5A (non-structural 5A protein), a component of complexes engaged in viral RNA synthesis, are detected at LD surfaces in infected cells. Interactions between the two proteins may be critical for anchoring RNA replication sites to droplets for initiating virus assembly. The requirements for targeting of core in particular has received considerable attention since the nature of its interaction with LDs could play a key role in determining the efficiency of virion production. As well as attaching to droplets, core is able to alter their intracellular distribution and direct them towards the microtubule organizing centre. Inhibitors that disrupt microtubules block this redistribution by core and there is a concomitant decrease in virus production. Therefore altered dynamics of LDs may contribute to HCV assembly and release. The purpose of targeting LDs by HCV may be linked to their contribution to the formation of VLDLs (very-low-density lipoproteins) in hepatocytes since virus circulating in infected patients is associated with lipoprotein. Thus HCV may utilize the role played by LDs in the formation of lipoprotein particles as part of its life cycle and access this pathway by direct interaction of viral components with these intracellular storage organelles.