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Study Elucidates a Mechanism for HCV Evasion of Immune Response

The authors of the study then utilized two computational modeling approaches to determine which E1E2 sequences are associated with HCVpp resistance to HC33.4 and AR4A. It was determined that changes at amino acid positions 242, 403, and 438 are important for determining sensitivity of HCV to bNAbs. To test the modeling predictions, the authors generated mutants using a site-directed mutagenesis approach and then tested these mutants for sensitivity to HC33.4 and AR4A, revealing that two polymorphisms, at positions 403 and 438, are modulators of resistance to both bNAbs.
To elucidate the mechanism by which these HCV variants modulate resistance to neutralizing antibodies, the authors examined binding of wild type and mutant HCV variants to scavenger receptor class B type I (SR-BI), which is a receptor known to play an important role in HCV entry into the cell. They determined that these two polymorphisms change binding to SR-B1, thereby demonstrating a new mechanism that HCV uses to evade the immune response.
Highlighting the importance of this work in illuminating how HCV manages to dodge the immune system, Dr. Bailey is quoted in the press release, “These are the mutations we believe may allow the viruses to avoid being blocked by antibodies altogether. If you think of it like a race, the antibody is trying to bind to the virus before it can enter the cell. We think this mutation may allow the virus to get into the cell before it even encounters the immune system.”
Samar Mahmoud graduated from Drew University in 2011 with a BA in biochemistry and molecular biology. After two years of working in industry as a quality control technician for a blood bank, she went back to school and graduated from Montclair State University in 2016 with a MS in pharmaceutical biochemistry. She is currently pursuing her PhD in molecular and cellular biology at the University of Massachusetts at Amherst.
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