"The inability to reproduce aspects of the hepatitis C virus life cycle in cell culture has slowed research progress on this important human pathogen," says senior author Charles M. Rice, Ph.D., Maurice R. and Corinne P. Greenberg Professor and head of the Laboratory of Virology and Infectious Disease at Rockefeller.
Like all viruses, HCV cannot replicate by itself; instead it takes over the machinery of a host cell to make copies of itself. Much about the life cycle of HCV remains poorly understood because scientists have been unable to reproduce an infectious form of HCV that they can observe in cell cultures.
"This system lays the foundation for future test tube studies of the virus life cycle and may help in the development of new drugs for combating HCV," adds Rice. "Our method replicates and produces virus particles that can infect new cells, initiating replication in them and leading to the production of more virus particles" says first author Brett Lindenbach, Ph.D., a postdoctoral fellow in Rice's lab
Lindenbach, Rice and their colleagues named their infectious cell culture virus HCVcc. Already HCVcc is yielding new knowledge about HCV. In a separate set of experiments, the researchers used HCVcc to confirm that a molecule called CD81, which sits on the surface of the human cell membrane, plays a crucial role in the entry of HCV.
Scientists have known that a protein produced by HCV, called E2, binds to CD81, and they believed that this interaction is necessary for the virus to bind to target cells. The Rockefeller researchers showed that CD81 molecules that are not attached to the surface of host cells compete with membrane-bound CD81 and inhibit entry of HCV into the cell. They also showed that HepG2 cells, which do not express CD81 but can support HCV RNA replication, could not be infected by HCVcc unless they express CD81.
MEDICA.de; Source: Rockefeller University