Genetically Associated CD16+56− Natural Killer Cell Interferon (IFN)–αR Expression Regulates Signaling and Is Implicated in IFN-α–Induced Hepatitis C Virus Decline
| Autor: | Nicole L. Yonkers, Gareth Hardy, Sara J. Conry, Donald D. Anthony, Perica Davitkov, Clifford V. Harding, Anita Compan, Qinglai Meng, Amy Hirsch, Benigno Rodriguez, Ronald E. Blanton, Julia M. Sugalski, Yngve Falck-Ytter |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Adult
Male Hepatitis C virus Alpha interferon Hepacivirus Receptor Interferon alpha-beta Biology GPI-Linked Proteins medicine.disease_cause Antiviral Agents Virus Natural killer cell Major Articles and Brief Reports Interferon medicine Humans Immunology and Allergy Cytotoxic T cell Aged Natural Cytotoxicity Triggering Receptor 3 Receptors IgG Interferon-alpha Hepatitis C Chronic Middle Aged medicine.disease Virology CD56 Antigen Lymphocyte Subsets Killer Cells Natural Chronic infection Treatment Outcome Infectious Diseases medicine.anatomical_structure Gene Expression Regulation Immunology Coinfection Female Signal Transduction medicine.drug |
| Zdroj: | The Journal of Infectious Diseases. 205:1131-1141 |
| ISSN: | 1537-6613 0022-1899 |
| DOI: | 10.1093/infdis/jis027 |
| Popis: | Acute hepatitis C virus (HCV) infection becomes persistent in a majority of cases [1], and the long-term risk of cirrhosis, liver failure, cancer, and mortality among those with chronic infection highlight the importance of effective therapy [1, 2]. HCV magnitude decrease at 4 and 12 weeks of pegylated interferon (IFN)–α plus ribavirin therapy is predictive of sustained virologic response [3]. Although mechanisms underlying IFN-α responsiveness remain unclear, factors associated with response to IFN-α therapy include HCV genotype, age, race, human immunodeficiency virus (HIV) coinfection, baseline HCV level, and polymorphism near the interleukin 28B (IL-28B) (IFN-λ3) gene locus [3–9]. Despite introduction of protease inhibitors, the need to combine these agents with IFN means that response to newer regimens continues to depend on factors regulating IFN-α responsiveness. Natural killer (NK) cells provide essential host defense during mouse hepatic viral [10, 11] and human herpesvirus infection [12–15]. They are innate lymphocytes with cytokine-producing, chemokine-producing, and cytotoxic activities regulated by activating and inhibitory receptors [16, 17]. Evidence for NK cells contributing to control of HCV derives from observations that genetically determined NK-KIR (Killer Immunoglobulin like Receptor)/ligand pairing correlates with the course of acute HCV infection [18] and that, during chronic infection, NK KIR2DL3, NKG2C, and NKp30 expression are associated with response to IFN-α–based therapy [19–21]. In addition, TRAIL expression is upregulated on NK cells during IFN-α–based therapy, and this correlates with in vitro cytolysis of HCV JFH-1–infected Huh 7.5 cells [22]. We observed NK IFN-αR and NKp30 expression to associate with IFN-α–dependent killer activity during HIV infection [23]. NK cells of individuals with preserved activity appeared to have enhanced IFN-αR expression. We hypothesized that IFN-αR expression is upregulated during chronic viral infection, in turn determining IFN-α–dependent function. Here, we evaluated NK cell subset IFN-αR and NKp30 expression in HCV genotype 1–infected patients at baseline, longitudinally over the course of IFN-α–based therapy, and in relation to IFN-α signaling capacity and viral decrease. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|