title: The GB virus C (GBV-C) NS3 serine protease inhibits HIV-1 replication in a CD4+ T lymphocyte cell line without decreasing HIV receptor expression.
abstract: BACKGROUND
  Persistent infection with GBV-C (GB Virus C), a non-pathogenic virus related to hepatitis C virus (HCV), prolongs survival in HIV infection. Two GBV-C proteins, NS5A and E2, have been shown previously to inhibit HIV replication in vitro. We investigated whether the GBV-C NS3 serine protease affects HIV replication.
  
  
  RESULTS
  GBV-C NS3 protease expressed in a human CD4+ T lymphocyte cell line significantly inhibited HIV replication. Addition of NS4A or NS4A/4B coding sequence to GBV-C NS3 increased the effect on HIV replication. Inhibition of HIV replication was dose-dependent and was not mediated by increased cell toxicity. Mutation of the NS3 catalytic serine to alanine resulted in loss of both HIV inhibition and protease activity. GBV-C NS3 expression did not measurably decrease CD4 or CXCR4 expression.
  
  
  CONCLUSIONS
  GBV-C NS3 serine protease significantly inhibited HIV replication without decreasing HIV receptor expression. The requirement for an intact catalytic serine at the active site indicates that inhibition was mediated by proteolytic cleavage of an unidentified target(s).
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, St. Louis University, St. Louis, Missouri, United States of America. georgesl@slu.edu
authors.forename: Sarah L
authors.initials: SL
authors.lastname: George
authors.forename: Dino
authors.initials: D
authors.lastname: Varmaz
authors.forename: John E
authors.initials: JE
authors.lastname: Tavis
authors.forename: Adnan
authors.initials: A
authors.lastname: Chowdhury
mesh_terms: D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000378:metabolism / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D029407:GB virus C / Q000201:enzymology* / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D016679:Genome, Viral / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D015728:Receptors, HIV / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D014162:Transfection; D017361:Viral Nonstructural Proteins / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects* / Q000235:genetics; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D019380:Anti-HIV Agents; D020365:RNA Helicases; D015728:Receptors, HIV; D012697:Serine Endopeptidases; D017361:Viral Nonstructural Proteins; C060028:NS3 protein, flavivirus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases