Scientists identify key interaction in hepatitis C virus

Dec 29, 2010

Scientists from the Florida campus of The Scripps Research Institute have identified a molecular interaction between a structural hepatitis C virus protein (HCV) and a protein critical to viral replication. This new finding strongly suggests a novel method of inhibiting the production of the virus and a potential new therapeutic target for hepatitis C drug development.

The study was published in the January 2010 issue (Volume 92, Part 1) of the Journal of General Virology.

These new data underline the essential role of the viral known as "core" as a primary organizer of the infectious HCV particle assembly and support a new molecular understanding of the formation of the viral particle itself.

"While our finding that the HCV core interacts with the non-structural helicase protein was not totally unexpected, this had not really been confirmed until this study," said Scripps Florida Professor Donny Strosberg, who led the study. "But the most exciting part is that small molecule inhibitors of dimerization [the joining of two identical subunits] of core actually inhibit interaction between core and helicase, thus possibly preventing production of an infectious viral particle."

A Viral Plague

Hepatitis C virus infects between 130 and 170 million people worldwide and is the cause of an epidemic of and cancer. Because current HCV treatments are only partially effective, a number of alternative are actively being pursued as possible drug targets.

One of the critical problems of finding inhibitors for the hepatitis C virus is that it mutates at such prodigious rates. An RNA virus such as hepatitis C can mutate at a rate estimated as high as one million times that of DNA viruses such as the .

With this in mind, Strosberg has been examining the core protein, the most conserved protein among all HCV genotypes. Core plays several essential roles in the viral cycle in the host cell. It is particularly important in the assembly of the hepatitis C nucleocapsid or capsid, an essential step in the formation of infectious viral particles; the nucleocapsid is the virus genome protected by a protein coat. By interacting with various structural and non-structural viral proteins, core plays an essential role in the HCV cycle during assembly and release of the infectious virus as well as disassembly of viral particles upon entering host cells. Core also interacts with a number of cellular proteins, possibly contributing to the disarmament of several host defense mechanisms and to the activation of oncogenic pathways.

Last year, Strosberg developed a novel quantitative test for monitoring these protein-protein interactions with the specific goal of identifying inhibitors of the core dimerization, which would block virus production. Strosberg and his colleagues uncovered peptides derived from the core protein of that inhibit not only dimerization of the core protein, but also production of the actual virus.

That earlier study led to the discovery of non-peptidic small organic molecules that strongly inhibited HCV production, one of which, SL201, was used in the new study.

In the new study, Strosberg and his colleagues focused on non-structural proteins that provide functions relating to HCV production, in particular NS3 helicase. The scientists' findings support a growing body of evidence that this protein participates in the assembly and production of infectious viral particles. The interaction of the core protein with this non-structural protein also confirms core as a key organizer of virus assembly and suggests it acts to facilitate the packaging and integration of the newly synthesized viral RNA.

Explore further: The impact of bacteria in our guts

More information: vir.sgmjournals.org/cgi/content/abstract/92/1/101

add to favorites email to friend print save as pdf

Related Stories

Scientists Model Hepatitis C Virus

May 25, 2007

One of the most common life-threatening viral infections in the United States today is hepatitis C virus (HCV). The standard treatment is successful in only about 50 percent of treated HCV chronic patients, with no effective ...

New strategy for inhibiting virus replication

Aug 14, 2009

Viruses need living cells for replication and production of virus progeny. Thus far, antiviral therapy primarily targets viral factors but often induces therapy resistance. New improved therapies attempt to targets cellular ...

Recommended for you

The impact of bacteria in our guts

19 hours ago

The word metabolism gets tossed around a lot, but it means much more than whether you can go back to the buffet for seconds without worrying about your waistline. In fact, metabolism is the set of biochemical ...

Stem cell therapies hold promise, but obstacles remain

20 hours ago

(Medical Xpress)—In an article appearing online today in the journal Science, a group of researchers, including University of Rochester neurologist Steve Goldman, M.D., Ph.D., review the potential and ch ...

New hope in fight against muscular dystrophy

21 hours ago

Research at Stockholm's KTH Royal Institute of Technology offers hope to those who suffer from Duchenne muscular dystrophy, an incurable, debilitating disease that cuts young lives short.

Biologists reprogram skin cells to mimic rare disease

Aug 21, 2014

Johns Hopkins stem cell biologists have found a way to reprogram a patient's skin cells into cells that mimic and display many biological features of a rare genetic disorder called familial dysautonomia. ...

User comments : 0