Hepatitis C virus (HCV) infection is an important risk factor for insulin resistance (IR). The latter is the pathogenic foundation underlying metabolic syndrome, steatosis and cirrhosis, and possibly hepatocellular ca...Hepatitis C virus (HCV) infection is an important risk factor for insulin resistance (IR). The latter is the pathogenic foundation underlying metabolic syndrome, steatosis and cirrhosis, and possibly hepatocellular carcinoma (HCC). The interplay between genetic and environmental risk factors ultimately leads to the development of IR. Obesity is considered a major risk factor, with dysregulation of levels of secreted adipokines from distended adipose tissue playing a major role in IR. HCV-induced IR may be due to the HCV core protein inducing proteasomal degradation of insulin receptor substrates 1 and 2, blocking intracellular insulin signaling. The latter is mediated by increased levels of both tumour necrosis factor-α (TNF-α) and suppressor of cytokine signaling 3 (SOC-3). IR, through different mechanisms, plays a role in the development of steatosis and its progression to steatohepatitis, cirrhosis and even HCC. In addition, IR has a role in impairing TNF signaling cascade, which in turn blocks STAT-1 translocation and interferon stimulated genes production avoiding the antiviral effect of interferon.展开更多
Hepatitis E virus (HEV) infection is a common causeof acute clinical hepatitis worldwide. HEV is an RNAcontainingvirus and the only member of the genusHepevirus in the family Hepeviridae . Human HEV isclassified into ...Hepatitis E virus (HEV) infection is a common causeof acute clinical hepatitis worldwide. HEV is an RNAcontainingvirus and the only member of the genusHepevirus in the family Hepeviridae . Human HEV isclassified into four genotypes widely distributed acrossthe world. The virus is mainly transmitted via the fecaloralroute, and water-borne epidemics have becomecharacteristic of hepatitis E in developing countries,including those in Latin America. The zoonoticpotential of HEV is broadly recognized. Thus, thereis an urgent need to re-evaluate virus transmissionscenarios and to enforce epidemiological surveillancesystems. Additionally, it is known that HEV infections,initially defined as self-limiting, can also take chroniccourses in immunocompromised patients. Moreover,we recently reported a high seroprevalence of HEV insamples from cirrhotic patients with no other etiologicalagents present, suggesting the potential role of HEVin the development of chronic liver illness. In thisreview, HEV genomic variability, transmission, chronicinfectious course, zoonotic potential and treatmentare discussed. Focus is placed on the impact of HEVinfection in Latin America, to support the developmentof specific control strategies and the handling of thisimportant and typically imperceptible viral infection.展开更多
AIM: To analyze the association of HCV-RNA with peripheral blood mononuclear cells (PBMC) and to answer the question whether HCV-RNA positivity in PBMC is due to viral replication. METHODS: HCV-RNA was monitored in se...AIM: To analyze the association of HCV-RNA with peripheral blood mononuclear cells (PBMC) and to answer the question whether HCV-RNA positivity in PBMC is due to viral replication. METHODS: HCV-RNA was monitored in serum and PBMC preparations from 15 patients with chronic HCV infection before, during and after an IFN-alpha therapy using a nested RT/PCR technique. In a second approach, PBMC from healthy donors were incubated in HCV positive plasma. RESULTS: In the IFN-alpha responding patients,HCV-RNA disappeared first from total RNA preparations of PBMC and then from serum. In contrast, in relapsing patients, HCV-RNA reappeared first in serum and then in PBMC. A quantitative analysis of the HCV-RNA concentration in serum was performed before and after transition from detectable to non detectable HCV-RNA in PBMC-RNA and vice versa. When HCV-RNA was detectable in PBMC preparations, the HCV concentration in serum was significantly higher than the serum HCV-RNA concentration when HCV-RNA in PBMC was not detectable. Furthermore, at no time during the observation period was HCV specific RNA observed in PBMC, if HCV-RNA in serum was under the detection limit. Incubation of PBMC from healthy donors with several dilutions of HCV positive plasma for two hours showed a concentration dependent PCR positivity for HCV-RNA in reisolated PBMC. CONCLUSION: The detectability of HCV-RNA in total RNA from PBMC seems to depend on the HCV concentration in serum. Contamination or passive adsorption by circulating virus could be the reason for detection of HCV-RNA in PBMC preparations of chronically infected patients.展开更多
Cytopathic “stealth-adapted” viruses bypass the cellular immune defense mechanisms because of molecular deletion or mutation of critical antigen coding genes. They, therefore, do not provoke the inflammatory reactio...Cytopathic “stealth-adapted” viruses bypass the cellular immune defense mechanisms because of molecular deletion or mutation of critical antigen coding genes. They, therefore, do not provoke the inflammatory reaction typical of infections with the conventional viruses from which stealth adapted viruses are derived. Stealth adapted viruses establish persistent, systemic virus infections, which commonly involve the brain. The brain damage can cause major mood and cognitive disorders, fatigue, seizures and various manifestations of an impaired autonomic nervous system. Symptoms can also result from: 1) induced autoimmunity, 2) antibody formation against virus antigens, 3) virus-induced cellular damage to non-brain tissues and 4) induced heightened overall immune reactivity, such that normally unrecognized components of the virus begin to become targeted by the cellular immune system. This last mechanism is relevant to the reported neurological and psychiatric adverse effects of vaccination in certain individuals. It is also appropriate to consider the infectious component of stealth adapted virus infections since family members and others may be at risk for becoming infected.展开更多
文摘Hepatitis C virus (HCV) infection is an important risk factor for insulin resistance (IR). The latter is the pathogenic foundation underlying metabolic syndrome, steatosis and cirrhosis, and possibly hepatocellular carcinoma (HCC). The interplay between genetic and environmental risk factors ultimately leads to the development of IR. Obesity is considered a major risk factor, with dysregulation of levels of secreted adipokines from distended adipose tissue playing a major role in IR. HCV-induced IR may be due to the HCV core protein inducing proteasomal degradation of insulin receptor substrates 1 and 2, blocking intracellular insulin signaling. The latter is mediated by increased levels of both tumour necrosis factor-α (TNF-α) and suppressor of cytokine signaling 3 (SOC-3). IR, through different mechanisms, plays a role in the development of steatosis and its progression to steatohepatitis, cirrhosis and even HCC. In addition, IR has a role in impairing TNF signaling cascade, which in turn blocks STAT-1 translocation and interferon stimulated genes production avoiding the antiviral effect of interferon.
文摘Hepatitis E virus (HEV) infection is a common causeof acute clinical hepatitis worldwide. HEV is an RNAcontainingvirus and the only member of the genusHepevirus in the family Hepeviridae . Human HEV isclassified into four genotypes widely distributed acrossthe world. The virus is mainly transmitted via the fecaloralroute, and water-borne epidemics have becomecharacteristic of hepatitis E in developing countries,including those in Latin America. The zoonoticpotential of HEV is broadly recognized. Thus, thereis an urgent need to re-evaluate virus transmissionscenarios and to enforce epidemiological surveillancesystems. Additionally, it is known that HEV infections,initially defined as self-limiting, can also take chroniccourses in immunocompromised patients. Moreover,we recently reported a high seroprevalence of HEV insamples from cirrhotic patients with no other etiologicalagents present, suggesting the potential role of HEVin the development of chronic liver illness. In thisreview, HEV genomic variability, transmission, chronicinfectious course, zoonotic potential and treatmentare discussed. Focus is placed on the impact of HEVinfection in Latin America, to support the developmentof specific control strategies and the handling of thisimportant and typically imperceptible viral infection.
基金Supported by a grant of DFG (SFB 402 Teilprojekt C1 (Mihm))by a grant of Hoffmann La Roche (Grenzach-Wyhden, Germany)Part of the data has been presented as poster at the 1999 EASL-meeting in Neaples
文摘AIM: To analyze the association of HCV-RNA with peripheral blood mononuclear cells (PBMC) and to answer the question whether HCV-RNA positivity in PBMC is due to viral replication. METHODS: HCV-RNA was monitored in serum and PBMC preparations from 15 patients with chronic HCV infection before, during and after an IFN-alpha therapy using a nested RT/PCR technique. In a second approach, PBMC from healthy donors were incubated in HCV positive plasma. RESULTS: In the IFN-alpha responding patients,HCV-RNA disappeared first from total RNA preparations of PBMC and then from serum. In contrast, in relapsing patients, HCV-RNA reappeared first in serum and then in PBMC. A quantitative analysis of the HCV-RNA concentration in serum was performed before and after transition from detectable to non detectable HCV-RNA in PBMC-RNA and vice versa. When HCV-RNA was detectable in PBMC preparations, the HCV concentration in serum was significantly higher than the serum HCV-RNA concentration when HCV-RNA in PBMC was not detectable. Furthermore, at no time during the observation period was HCV specific RNA observed in PBMC, if HCV-RNA in serum was under the detection limit. Incubation of PBMC from healthy donors with several dilutions of HCV positive plasma for two hours showed a concentration dependent PCR positivity for HCV-RNA in reisolated PBMC. CONCLUSION: The detectability of HCV-RNA in total RNA from PBMC seems to depend on the HCV concentration in serum. Contamination or passive adsorption by circulating virus could be the reason for detection of HCV-RNA in PBMC preparations of chronically infected patients.
文摘Cytopathic “stealth-adapted” viruses bypass the cellular immune defense mechanisms because of molecular deletion or mutation of critical antigen coding genes. They, therefore, do not provoke the inflammatory reaction typical of infections with the conventional viruses from which stealth adapted viruses are derived. Stealth adapted viruses establish persistent, systemic virus infections, which commonly involve the brain. The brain damage can cause major mood and cognitive disorders, fatigue, seizures and various manifestations of an impaired autonomic nervous system. Symptoms can also result from: 1) induced autoimmunity, 2) antibody formation against virus antigens, 3) virus-induced cellular damage to non-brain tissues and 4) induced heightened overall immune reactivity, such that normally unrecognized components of the virus begin to become targeted by the cellular immune system. This last mechanism is relevant to the reported neurological and psychiatric adverse effects of vaccination in certain individuals. It is also appropriate to consider the infectious component of stealth adapted virus infections since family members and others may be at risk for becoming infected.
