Evolution of the hypervariable region of hepatitis C virus.

Despite being the most intensively studied part of the hepatitis C virus genome, our understanding of the function of the hypervariable region (HVR) at the NH2-terminus of the E2 protein remains very limited. During chronic infection the HVR usually changes over time, with changes usually mirrored by those of HVR-specific antibodies. Evidence is presented suggesting that the HVR is subject to constraint in its length, amino acid composition, and in the amino acid replacements that are tolerated at different positions. These constraints, and the pattern of HVR variation during chronic infection, suggest that it has an important role in virus infection. A causal relationship between HVR variation and persistence of HCV remains to be demonstrated.