AIM: Chemokines and their receptors are crucial for immune responses in HCV and HIV infection. RANTES gene polymorphisms lead to altered gene expression and influence the natural course of HIV infection. Therefore,the...AIM: Chemokines and their receptors are crucial for immune responses in HCV and HIV infection. RANTES gene polymorphisms lead to altered gene expression and influence the natural course of HIV infection. Therefore,these mutations may also affect the course of HIV/HCV coinfection.METHODS: We determined allele frequencies of RANTES-403 (G→A), RANTES-28 (C→G) and RANTESIN1.1 (T→C) polymorphisms using real-time PCR and hybridization probes in patients with HIV (n = 85), HCV (n= 112), HIV/HCV coinfection (n = 121), and 109 healthy controls. Furthermore, HIV and HCV loads as well as CD4+ and CD8+ cell counts were compared between different RANTES genotypes.RESULTS: Frequencies of RANTES-403 A, RANTES-28 G and RANTES-IN1.1 C alleles were higher in HIV infected patients than in healthy controls (-403: 28.2% vs 15.1%,P = 0.002; -28: 5.4% vs 2.8%, not significant; IN1.1:19.0% vs 11.0%, P = 0.038). In HIV/HCV coinfected patients, these RANTES alleles were less frequent than in patients with HIV infection alone (15.4% P = 0.002;1.7%; P = 0.048; 12.0%; not significant). Frequencies of these alleles were not significantly different between HIV/HCV positive patients, HCV positive patients and healthy controls.CONCLUSION: All three RANTES polymorphisms showed increased frequencies of the variant allele exclusively in patients with HIV monoinfection. The finding that the frequencies of these alleles remained unaltered in HIV/HCV coinfected patients suggests that HCV coinfection interferes with selection processes associated with these alleles in HIV infection.展开更多
Hepatitis C virus(HCV)frequently elicits only mild immune responses so that it can often establish chronic infection.In this case HCV antigens persist and continue to stimulate the immune system.Antigen persistence th...Hepatitis C virus(HCV)frequently elicits only mild immune responses so that it can often establish chronic infection.In this case HCV antigens persist and continue to stimulate the immune system.Antigen persistence then leads to profound changes in the infected host’s immune responsiveness,and eventually contributes to the pathology of chronic hepatitis.This topic highlight summarizes changes associated with chronic hepatitis C concerning innate immunity(interferons,natural killer cells),adaptive immune responses(immunoglobulins,T cells,and mechanisms of immune regulation(regulatory T cells).Our overview clarifies that a strong anti-HCV immune response is frequently associated with acute severe tissue damage.In chronic hepatitis C,however,the effector arms of the immune system either become refractory to activation or take over regulatory functions.Taken together these changes in immunity may lead to persistent liver damage and cirrhosis.Consequently,effector arms of the immune system will not only be considered with respect to antiviral defence but also as pivotal mechanisms of inflammation,necrosis and progression to cirrhosis.Thus,avoiding Scylla-a strong,sustained antiviral immune response with inital tissue damage-takes the infected host to virus-triggered immunopathology,which ultimately leads to cirrhosis and liver cancerthe realm of Charybdis.展开更多
文摘AIM: Chemokines and their receptors are crucial for immune responses in HCV and HIV infection. RANTES gene polymorphisms lead to altered gene expression and influence the natural course of HIV infection. Therefore,these mutations may also affect the course of HIV/HCV coinfection.METHODS: We determined allele frequencies of RANTES-403 (G→A), RANTES-28 (C→G) and RANTESIN1.1 (T→C) polymorphisms using real-time PCR and hybridization probes in patients with HIV (n = 85), HCV (n= 112), HIV/HCV coinfection (n = 121), and 109 healthy controls. Furthermore, HIV and HCV loads as well as CD4+ and CD8+ cell counts were compared between different RANTES genotypes.RESULTS: Frequencies of RANTES-403 A, RANTES-28 G and RANTES-IN1.1 C alleles were higher in HIV infected patients than in healthy controls (-403: 28.2% vs 15.1%,P = 0.002; -28: 5.4% vs 2.8%, not significant; IN1.1:19.0% vs 11.0%, P = 0.038). In HIV/HCV coinfected patients, these RANTES alleles were less frequent than in patients with HIV infection alone (15.4% P = 0.002;1.7%; P = 0.048; 12.0%; not significant). Frequencies of these alleles were not significantly different between HIV/HCV positive patients, HCV positive patients and healthy controls.CONCLUSION: All three RANTES polymorphisms showed increased frequencies of the variant allele exclusively in patients with HIV monoinfection. The finding that the frequencies of these alleles remained unaltered in HIV/HCV coinfected patients suggests that HCV coinfection interferes with selection processes associated with these alleles in HIV infection.
文摘Hepatitis C virus(HCV)frequently elicits only mild immune responses so that it can often establish chronic infection.In this case HCV antigens persist and continue to stimulate the immune system.Antigen persistence then leads to profound changes in the infected host’s immune responsiveness,and eventually contributes to the pathology of chronic hepatitis.This topic highlight summarizes changes associated with chronic hepatitis C concerning innate immunity(interferons,natural killer cells),adaptive immune responses(immunoglobulins,T cells,and mechanisms of immune regulation(regulatory T cells).Our overview clarifies that a strong anti-HCV immune response is frequently associated with acute severe tissue damage.In chronic hepatitis C,however,the effector arms of the immune system either become refractory to activation or take over regulatory functions.Taken together these changes in immunity may lead to persistent liver damage and cirrhosis.Consequently,effector arms of the immune system will not only be considered with respect to antiviral defence but also as pivotal mechanisms of inflammation,necrosis and progression to cirrhosis.Thus,avoiding Scylla-a strong,sustained antiviral immune response with inital tissue damage-takes the infected host to virus-triggered immunopathology,which ultimately leads to cirrhosis and liver cancerthe realm of Charybdis.
