Impact of the genetic restriction of virus-specific T-cell responses in hepatitis C virus infection

M ore than 4 million women and men in the United States and 150 million people worldwide are estimated to be hepatitis C virus (HCV) seropositive. 1,2 Most of these individuals are chronically infected with the virus and are at high risk of cirrhosis, hepatocellular carcinoma, and liverrelated death. The natural history of HCV infection, however, is highly variable. Some individuals do not become HCV infected despite high levels of exposure. 3 Other individuals may clear HCV RNA following acute infection, and whereas some individuals with long-term HCV viremia remain clinically asymptomatic, others have progressive disease. 4 Indeed, marked variability in natural history is seen even among groups of individuals with single-source exposure to HCV, as occurred in a population of Irish women exposed to HCV-contaminated anti-D immune globulin. 5 Together these observations suggest that host factors, particularly host immune response, play a key role in the regulation of HCV pathogenesis.

show abstract

“…We additionally examined the references cited in each paper, including several review papers. (6;7;19;20)…”

Section: Methodsmentioning

confidence: 99%

Specific human leukocyte antigen class I and II alleles associated with hepatitis C virus viremia

et al. 2009

View full text Add to dashboard Cite

show abstract

“…HLA class I molecules are recognized by NK cells through killer immunoglobulin-like receptors (KIR) [17,18]. Recent studies have indicated that an HLA-class I/KIR complex is associated with the pathogenesis and susceptibility of type-1 diabetes mellitus [19,20,21], psoriatic arthritis [22], ankylosing spondylitis [23], hepatitis B [24], and hepatitis C [25]. In particular, the HLA-C/KIR complex has been investigated in context of many autoimmune diseases, infections and connective disorders.…”

Section: Discussionmentioning

confidence: 99%

Association of HLA Alleles with Autoimmune Thyroid Disease in Korean Children

et al. 2011

View full text Add to dashboard Cite

Backgrounds: Data regarding genetics of Hashimoto’s disease (HD) and Graves’ disease (GD) in Korean children are lacking. Methods: 73 patients with autoimmune thyroid disease (AITD; HD 32, GD 41) were recruited. We analyzed human leukocyte antigen (HLA) class I and HLA-DRB1 by PCR-SSP, and compared them with those of 159 controls. Results: In AITD, the allele frequencies of HLA-A*02, -B*46, -Cw*01 and -DRB1*08 were higher and those of HLA-A*30, -B*07, -Cw*07 and -DRB1*01 were lower than in controls. In HD, those of HLA-B*46 and -Cw*01 were higher and those of HLA-DRB1*01 and -Cw*07 were lower than in controls. In GD, those of HLA-A*02, -B*46, -Cw*01 and -DRB1*08 were higher and those of HLA-DRB1*07 and -Cw*07 were lower than in controls. Between HD and GD, there were no significant differences in allele frequencies. The risk of AITD in the presence of both HLA-B*46 and -Cw*01 is higher than in the presence of either allele alone. Conclusion: The susceptible and protectable alleles in HD are similar to those in GD. Coexistence of HLA-B*46 and -Cw*01 may be a genetic gene marker for early-onset AITD in Koreans.

show abstract

“…It has, therefore, been suggested that different HLA class I alleles are associated with differential outcomes of HCV infection, e.g. viral clearance versus persistence [109] . Analysis of the role of HLA alleles in viral infections are hindered by multiple factors, including the wide polymorphism of HLA alleles, their association with other genetic characteristics e.g.…”

Section: Role Of the Host Hla Classⅰmentioning

confidence: 99%

Host and viral factors contributing to CD8+ T cell failure in hepatitis C virus infection

Neumann‐Haefelin

Spangenberg²,

Blum³

et al. 2007

WJG

View full text Add to dashboard Cite

Virus-specific CD8+ T cells are thought to be the major anti-viral effector cells in hepatitis C virus (HCV) infection. Indeed, viral clearance is associated with vigorous CD8+ T cell responses targeting multiple epitopes. In the chronic phase of infection, HCV-specific CD8+ T cell responses are usually weak, narrowly focused and display often functional defects regarding cytotoxicity, cytokine production, and proliferative capacity. In the last few years, different mechanisms which might contribute to the failure of HCV-specific CD8+ T cells in chronic infection have been identified, including insufficient CD4+ help, deficient CD8+ T cell differentiation, viral escape mutations, suppression by viral factors, inhibitory cytokines, inhibitory ligands, and regulatory T cells. In addition, host genetic factors such as the host's human leukocyte antigen (HLA) background may play an important role in the efficiency of the HCV-specific CD8+ T cell response and thus outcome of infection. The growing understanding of the mechanisms contributing to T cell failure and persistence of HCV infection will contribute to the development of successful immunotherapeutical and -prophylactical strategies.

show abstract

Impact of the genetic restriction of virus-specific T-cell responses in hepatitis C virus infection

Cited by 27 publications

References 117 publications

Specific human leukocyte antigen class I and II alleles associated with hepatitis C virus viremia

Specific human leukocyte antigen class I and II alleles associated with hepatitis C virus viremia

Association of HLA Alleles with Autoimmune Thyroid Disease in Korean Children

Host and viral factors contributing to CD8+ T cell failure in hepatitis C virus infection

Contact Info

Product

Resources

About