Scientists find a key to hepatitis C entry into cells
Understanding structure of HCV proteins could aid in vaccine development
Date:
September 21, 2021
Source:
NIH/National Institute of Allergy and Infectious Diseases
Summary:
Scientists describe the structure of a key protein on the surface of
the hepatitis C virus (HCV) and how it interacts with its receptor
found on some human cells. The findings provide new leads for
developing an HCV vaccine.
FULL STORY ==========================================================================
In a new paper published in Nature, scientists from the National
Institute of Allergy and Infectious Diseases (NIAID), part of the
National Institutes of Health, describe the structure of a key protein
on the surface of the hepatitis C virus (HCV) and how it interacts with
its receptor found on some human cells.
The findings provide new leads for developing an HCV vaccine. Hepatitis
C is one of the most common bloodborne infections in the United
States. Although it may not cause any symptoms in its early stages,
untreated chronic infections can lead to severe liver damage, cancer,
and death. Concerningly, infections are on the rise among young adults,
largely due to exposure resulting from shared drug-injectables. No
vaccine is available to prevent HCV infection.
==========================================================================
HCV is usually transmitted via blood, such as during birth or when drug- injection equipment is shared. Because HCV may not cause any symptoms for
years after initial infection, infections often go undetected. According
to the U.S.
Centers for Disease Control and Prevention, an estimated 2.4 million
people are living with hepatitis C infection in the United States. More
than half of all people infected with HCV are thought to develop chronic infection. HCV is a leading cause of cirrhosis, liver failure requiring transplant, and the leading cause of death from liver disease. Although effective antiviral drugs are available to treat HCV infection, they
are expensive and do not prevent reinfection.
In their new paper in Nature, researchers from NIAID and other
organizations describe the interaction between a protein expressed on the surface of the HCV, known as HCV E2, and a receptor called CD81 found on
the surface of some human cells. Prior research had shown that antibodies interfered with interactions between these two proteins. This suggested
that the interaction between HCV E2 and CD81 allowed HCV to enter and
infect human cells. However, exactly how this occurred was unknown.
The researchers determined the exact structure of HCV E2 and CD81 and
studied how the two proteins interacted when exposed to each other under different conditions. They found that under acidic conditions, HCV E2
easily binds to the CD81 receptor. Once the interaction between virus
and receptor begins, HCV E2 changes shape, facilitating its entrance into
the cell by putting the virus in closer contact with the cell membrane.
Identifying these structures and the ways they interact with each other
may provide the foundation for a vaccine against HCV, the researchers
say. A vaccine potentially could cause a person to make specific
antibodies that prevent HCV E2 from binding with CD81, stopping the
virus from entering the cell, and preventing HCV infection.
========================================================================== Story Source: Materials provided by NIH/National_Institute_of_Allergy_and_Infectious Diseases. Note: Content
may be edited for style and length.
========================================================================== Journal Reference:
1. Ashish Kumar, Reafa A. Hossain, Samantha A. Yost, Wei Bu,
Yuanyuan Wang,
Altaira D. Dearborn, Arash Grakoui, Jeffrey I. Cohen, Joseph
Marcotrigiano. Structural insights into hepatitis C virus receptor
binding and entry. Nature, 2021; DOI: 10.1038/s41586-021-03913-5 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2021/09/210921125116.htm
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