Activating the innate immune response to counter chronic hepatitis B virus infection.
Chronic infection with hepatitis B virus (HBV) is endemic to several populous parts of the world, where resulting complicating cirrhosis and hepatocellular carcinoma occur commonly. Licensed drugs to treat the infection have limited curative efficacy, and development of therapies that eliminate all replication intermediates of HBV is a priority. Areas covered: The recent demonstration that the activation of the innate immune response may eradicate HBV from infected hepatocytes has a promising therapeutic application. Small molecule stimulators of Toll-like receptors (TLRs) inhibit replication of woodchuck hepatitis virus in woodchucks and HBV in chimpanzees and mice. Early stage clinical trials using GS-9620, a TLR7 agonist, indicate that this candidate antiviral is well tolerated in humans. Using an alternative approach, triggering the innate immune response with agonists of lymphotoxin-β receptor caused efficient APOBEC-mediated deamination and degradation of viral covalently closed circular DNA. Expert opinion: Eliminating HBV cccDNA from infected individuals would constitute a cure, and has become the focus of intensive research that employs various therapeutic approaches, including gene therapy. Immunomodulation through innate immune activation shows promise for the treatment of chronic infection of HBV (CHB) and, used in combination with other therapeutics, may contribute to the global control of infections and ultimately to the eradication of HBV.
a Wits/SAMRC Antiviral Gene Therapy Research Unit, School of Pathology, Faculty of Health Sciences , University of the Witwatersrand , Johannesburg , South Africa.
Camilla
C
Lamb
a Wits/SAMRC Antiviral Gene Therapy Research Unit, School of Pathology, Faculty of Health Sciences , University of the Witwatersrand , Johannesburg , South Africa.
Patrick
P
Arbuthnot
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D004261:DNA Replication / Q000502:physiology; D004279:DNA, Viral / Q000276:immunology / Q000378:metabolism; D006515:Hepatitis B virus / Q000187:drug effects* / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000502:physiology*; D056747:Immunomodulation / Q000187:drug effects / Q000502:physiology; D011621:Pteridines / Q000494:pharmacology / Q000627:therapeutic use; D051199:Toll-Like Receptor 7 / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology
D000998:Antiviral Agents; D004279:DNA, Viral; D011621:Pteridines; D051199:Toll-Like Receptor 7; C582524:vesatolimod
Cccdna; HBV; Toll like receptor; cytokines; immunotherapy; interferon