Chronic hepatitis B virus (HBV) infection is a major cause of chronic liver disease and cancer worldwide. The mechanisms of viral genome sensing and the evasion of innate immune responses by HBV infection are still poorly understood. Recently, the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) was identified as a DNA sensor. In this study, we investigated the functional role of cGAS in sensing HBV infection and elucidate the mechanisms of viral evasion. We performed functional studies including loss-of-function and gain-of-function experiments combined with cGAS effector gene expression profiling in an infectious cell culture model, primary human hepatocytes, and HBV-infected human liver chimeric mice. Here, we show that cGAS is expressed in the human liver, primary human hepatocytes, and human liver chimeric mice. While naked relaxed-circular HBV DNA is sensed in a cGAS-dependent manner in hepatoma cell lines and primary human hepatocytes, host cell recognition of viral nucleic acids is abolished during HBV infection, suggesting escape from sensing, likely during packaging of the genome into the viral capsid. While the hepatocyte cGAS pathway is functionally active, as shown by reduction of viral covalently closed circular DNA levels in gain-of-function studies, HBV infection suppressed cGAS expression and function in cell culture models and humanized mice. Conclusion: HBV exploits multiple strategies to evade sensing and antiviral activity of cGAS and its effector pathways.

• MeSH
• buněčné kultury MeSH
• DNA virů imunologie   MeSH
• hepatitida B imunologie   patofyziologie   MeSH
• hepatocyty metabolismus   virologie   MeSH
• hybridizace in situ fluorescenční metody   MeSH
• imunitní únik imunologie   fyziologie   MeSH
• interakce hostitele a patogenu MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• lidé MeSH
• myši MeSH
• nukleotidy cyklické metabolismus   MeSH
• stanovení celkové genové exprese metody   MeSH
• virus hepatitidy B patogenita   MeSH
• western blotting MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• cyclic guanosine monophosphate-adenosine monophosphate MeSH Prohlížeč
• DNA virů MeSH
• nukleotidy cyklické MeSH

In this study we evaluate the prevalence of HBV and HCV infections and the HBV and/or HCV viral load as well as HCV genotype among 737 HIV-infected patients. 89/737 (12.1%) were HBsAg(+) and the majority of them (60.7%) were HBeAg(+), in contrast to general Greek population; anti-HBc seropositivity was detected in 48.1% of the study population. Serum HBV-DNA levels were 5.75 +/- 1.66 (-log 10 copies/ml) and HBeAg(+) coinfected patients had significantly higher levels than HBeAg(-) ones (7.40 +/- 0.64 vs 4.59 +/- 1.01, respectively, p < 0.001). 8.2% of HIV-infected patients were anti-HCV(+) and the majority of them (85.7%) had HCV-RNA levels more than 700.000 IU/I. The most common HCV-genotype was genotype-1 (12/28, 42.9%), representing a difficult-to-treat special population.

• MeSH
• Hepacivirus izolace a purifikace   patogenita   MeSH
• hepatitida B epidemiologie   MeSH
• hepatitida C epidemiologie   MeSH
• HIV séropozitivita * MeSH
• komorbidita MeSH
• lidé MeSH
• retrospektivní studie MeSH
• sérologické testy MeSH
• virová nálož MeSH
• virus hepatitidy B izolace a purifikace   patogenita   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Řecko epidemiologie   MeSH

The aim of this study was to evaluate the efficacy of alpha-interferon (alpha-IFN) treatment of 56 chronic hepatitis B (HB) patients positive for HB e antigen (HBeAg), which were previously not treated with alpha-IFN (group A). Seven of them, which did not respond to initial alpha-IFN treatment, were subjected to additional treatment with alpha-IFN (group B). Another 7 patients with chronic HB caused apparently by an HBeAg-minus HB virus (HBV) mutant represented group C. In the alpha-IFN treatment, 5 megaunits (MU) of alpha-IFN were administered subcutaneously three times a week for six months. A trend of improvement of important markers of the disease in the treated patients could be seen with increasing time after completion of the treatment even though it was not statistically significant. In group A, the absence of serum HBV DNA was found in 43% of the patients at the end of the treatment, in 41% 6 months later, and in 46% 12 months later. At the same time intervals group A showed negative HBeAg in 36%, 39% and 46%, positive anti-HBeAg in 36%, 38%, and 46%, negative HBsAg in 9%, 11%, and 14%, and normal level of alanine transaminase (ALT) in 23%, 39%, and 44%, respectively. A trend toward better results of alpha-interferon therapy for the group A patients displaying lower baseline viremia and higher ALT activity could be seen; however, this relationship was not statistically significant. Groups B and C were too small for statistical analysis. Nevertheless, 4 of 7 patients of group B were negative for HBV DNA 12 months after the treatment and HBV DNA was eliminated during the treatment in all patients of group C; however, 3 patients relapsed after the treatment.

• MeSH
• alanintransaminasa analýza   metabolismus   MeSH
• antivirové látky terapeutické užití   MeSH
• chronická hepatitida B farmakoterapie   MeSH
• hepatitida B - antigeny e chemie   genetika   MeSH
• interferon alfa terapeutické užití   MeSH
• lidé MeSH
• mutace * MeSH
• viremie krev   MeSH
• virus hepatitidy B účinky léků   patogenita   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• Názvy látek
• alanintransaminasa MeSH
• antivirové látky MeSH
• hepatitida B - antigeny e MeSH
• interferon alfa MeSH

• MeSH
• dospělí MeSH
• Downův syndrom epidemiologie   etiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• věk matky MeSH
• věkové faktory MeSH
• virus hepatitidy B patogenita   MeSH
• vystavení vlivu životního prostředí MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Austrálie MeSH
• Československo MeSH
• Japonsko MeSH
• Spojené království MeSH