Researchers have discovered a means to interrupt replication of hepatitis B virus by blocking the ribonuclease H (RNAseH) enzyme, which had previously eluded investigators. The breakthrough may lead to new drugs that can help suppress the virus enough to cure hepatitis B, reported John Tavis, Ph.D., Saint Louis University professor of molecular microbiology and immunology.
The hepatitis B virus replicates by reverse transcription, a process in which two essential viral enzymes convert viral DNA to RNA and then back to DNA. Researchers have successfully assayed the first enzyme—a DNA polymerase—and developed five US Food and Drug Administration-approved drugs to target the enzyme. Although these drugs can suppress hepatitis B for a long time, the virus can multiply again years later, so hepatitis B-infected people must follow an expensive drug regimen for decades.
Travis searched for 19 years for a way to measure RNAseH—the other enzyme necessary for hepatitis B replication—and devise ways to block it. The research team benefited from research breakthroughs with HIV, which replicates through a similar reverse transcription process. The team’s next task will be to study and measure other genotypes of the hepatitis B virus and to “improve the strength and speed of the RNAseH assay for high throughput screening….” Success with these tasks would clear the way for development and testing of drugs targeting RNAseH, which could combine with existing drugs to suppress hepatitis B completely.
More than 350 million people worldwide have chronic hepatitis B, the principal cause of liver cancer. More than 1 million hepatitis B-infected people die from liver disease or liver cancer annually.
The full report, “The Hepatitis B Virus Ribonuclease H Is Sensitive to Inhibitors of the Human Immunodeficiency Virus Ribonuclease H and Integrase Enzymes,” was published online in the journal PLOS Pathogens (2013; doi:10.1371/journal.ppat.1003125).