Scientists shed light on mystery surrounding hepatitis B virus: Discovery is decades in the making

January 9, 2013, National Institutes of Health

(Medical Xpress)—Scientists from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), part of the National Institutes of Health, and the University of Oxford, U.K., have shed light on a long-standing enigma about the structure of a protein related to the Hepatitis B virus. Their findings, reported in Structure, could lead to new therapeutic strategies for chronic liver disease.

World-wide, some 350 million people are chronically infected with (HBV), of whom 620,000 die each year from HBV-related liver disease. Like any other pathogen, HBV expresses that trigger the body's immune system to defend itself. A relatively small and simple virus, HBV has three major clinical antigens that elicit an immune response: the surface antigen (which is also used safely and effectively to vaccinate individuals against HBV), the core antigen (HBcAg), and the e-antigen (HBeAg).

The HBV core antigen and the e-antigen are basically two versions of the same protein, but the core antigen is important for , while the e-antigen is not. The e-antigen plays a role in establishing and . In addition, the core antigen assembles into the shell (capsid) that houses the genetic material of the virus, while the e-antigen is secreted into the bloodstream in an unassembled form. The relationship between the e-antigen and the core antigen has been a mystery for the past three decades.

In the new study, the NIH scientists developed a unique antibody that binds to and forms a stable complex with e-antigen. This complex was found to form well-diffracting crystals whose analysis allowed the structure of the complex to be determined. They discovered that the e-antigen subunit has essentially the same fold as the core antigen subunit, but that it pairs into dimers (two associated subunits) in an entirely different way, with a relative rotation of 140 degrees between the subunits. The rotation obviates the protein's ability to assemble and transforms its antigenic character. This switch represents a novel mechanism for regulating a protein's structure and function.

Understanding the e-antigen structure provides a framework upon which future studies can build to fully elucidate its role in HBV persistence and possibly a way to prevent the establishment of chronic liver infections. For more information, visit www.niams.nih.gov/News_and_Eve … 2013/hepatitis_b.asp.

Explore further: Earlier treatment for young patients with chronic hepatitis B more effective in clearing virus

Related Stories

Earlier treatment for young patients with chronic hepatitis B more effective in clearing virus

September 6, 2012
Scientists from A*STAR's Singapore Institute for Clinical Sciences (SICS), together with clinical collaborators from London , discovered for the first time that children and young patients with chronic Hepatitis B Virus infection ...

Recommended for you

More surprises about blood development—and a possible lead for making lymphocytes

January 22, 2018
Hematopoietic stem cells (HSCs) have long been regarded as the granddaddy of all blood cells. After we are born, these multipotent cells give rise to all our cell lineages: lymphoid, myeloid and erythroid cells. Hematologists ...

How metal scaffolds enhance the bone healing process

January 22, 2018
A new study shows how mechanically optimized constructs known as titanium-mesh scaffolds can optimize bone regeneration. The induction of bone regeneration is of importance when treating large bone defects. As demonstrated ...

Bioengineered soft microfibers improve T-cell production

January 18, 2018
T cells play a key role in the body's immune response against pathogens. As a new class of therapeutic approaches, T cells are being harnessed to fight cancer, promising more precise, longer-lasting mitigation than traditional, ...

Weight flux alters molecular profile, study finds

January 17, 2018
The human body undergoes dramatic changes during even short periods of weight gain and loss, according to a study led by researchers at the Stanford University School of Medicine.

Secrets of longevity protein revealed in new study

January 17, 2018
Named after the Greek goddess who spun the thread of life, Klotho proteins play an important role in the regulation of longevity and metabolism. In a recent Yale-led study, researchers revealed the three-dimensional structure ...

The HLF gene protects blood stem cells by maintaining them in a resting state

January 17, 2018
The HLF gene is necessary for maintaining blood stem cells in a resting state, which is crucial for ensuring normal blood production. This has been shown by a new research study from Lund University in Sweden published in ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.