bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of gene transcription in sera during chronic hepatitis C infection
Authors: Carpentier Arnaud , Conti Filoména , Carrière Matthieu , Aoudjehane Lynda , Miroux Céline , Moralès Olivier , Calmus Yvon , Groux Hervé , Auriault Claude , Pancré Véronique , Delhem Nadira , Podevin Philippe 
Published: January 2009

AbstractAlternative, non‐invasive techniques are necessary to monitor the progression of liver disease during chronic hepatitis C. Firstly, because serum is the most accessible material for studies using qPCR in microplates, gene transcription was compared in 219 selected genes involved in the pathogenesis of hepatitis C virus (HCV) infection between sera, PBMCs and liver samples collected simultaneously from five patients infected chronically. Secondly, using sera, gene profiles were compared between HCV‐infected patients (n = 10) and healthy controls (n = 10). In addition, the influence of alcohol intake was examined in patients infected with HCV genotype‐1. Firstly, amplifiable mRNAs were obtained in all samples. After amplification, significant correlations were observed between: liver versus serum; liver versus PBMCs; and serum versus PBMCs (r2 = 0.37, r2 = 0.54, r2 = 0.49, respectively). A comparison of gene transcription by gene involved in T‐ and B‐cell markers, adhesion molecules, apoptosis, liver matrix turnover and inflammation, revealed comparable, significant correlations between serum and liver, (r2 = 0.30, r2 = 0.60, r2 = 0.51, r2 = 0.51, r2 = 0.26, and r2 = 0.61 respectively). Secondly, a quantitative analysis of gene expression in sera between genotype‐1b‐infected patients and healthy controls revealed that 41 genes involved closely in T‐cell activation and apoptosis were over‐expressed significantly in patients infected with HCV. In these patients, alcohol consumption was associated with an increased expression of six genes involved in the inflammatory response, together with a decrease of genes associated with dendritic cell function. It is concluded that in patients infected with HCV, serum can be used to evaluate expression of liver genes. Further prospective studies are clearly needed to validate the initial results and to define the relevant genes. J. Med. Virol. 81:473–480, 2009. © 2009 Wiley‐Liss, Inc.
A matched case‐controlled study of 48 and 72 weeks of peginterferon plus ribavirin combination therapy in patients infected with HCV genotype 1b in Japan: amino acid substitutions in HCV core region as predictor of sustained virological response
Authors: Akuta Norio , Suzuki Fumitaka , Hirakawa Miharu , Kawamura Yusuke , Yatsuji Hiromi , Sezaki Hitomi , Suzuki Yoshiyuki , Hosaka Tetsuya , Kobayashi Masahiro , Kobayashi Mariko , Saitoh Satoshi , Arase Yasuji , Ikeda Kenji , Kumada Hiromitsu 
Published: January 2009

AbstractSubstitution of amino acid (aa) 70 and 91 in the core region of HCV genotype 1b is a useful pretreatment predictor of efficacy of 48‐week peginterferon (PEG‐IFN) plus ribavirin (RBV) therapy. Here, we determined the efficacy of 72‐week PEG‐IFN/RBV and the predictive factors to such therapy in a case–control study matched for sex, age, and periods from the start of treatment to initial point of HCV RNA‐negative. We compared the treatment efficacy of 72‐week regimen in 65 patients with that of 48‐week in 130 patients, who were infected with HCV genotype 1b and treated with PEG‐IFN/RBV. They consisted mainly of late virological responders (LVR) (HCV RNA‐positive at 12 weeks and negative at 24 weeks after start of treatment). Sustained virological response (SVR) was achieved by 61.5% and 32.3% of patients of the 72‐ and 48‐week groups, respectively, while non‐virological response was noted in 9.2% and 29.2% of the respective groups. Multivariate analysis identified substitution of aa 70 and 91 (Arg70 and/or Leu91) and duration of treatment (72‐week) as independent parameters that significantly influenced SVR. For Arg70 and/or Leu91 of core region, SVR rate was significantly higher in 72‐ (68.0%) than 48‐week group (37.8%). For wild‐type of ISDR, SVR rate was significantly higher in 72‐ (61.2%) than in 48‐week group (29.3%). We conclude that 72‐week PEG‐IFN/RBV improves SVR rate for LVR, especially those with Arg70 and/or Leu91 of core region or wild‐type of ISDR. Substitution of aa 70 and 91 is also a useful pretreatment predictor of response to 72‐week PEG‐IFN/RBV. J. Med. Virol. 81:452–458, 2009. © 2009 Wiley‐Liss, Inc.
Susceptibility of hepatitis B virus to lamivudine restored by resistance to adefovir
Authors: Zaaijer H.L. , Takkenberg R.B. , Weegink C.J. , Rebers S.P.H. , Menting S. , Reesink H.W. , Schinkel J. , Molenkamp R. 
Published: January 2009

AbstractSerial monotherapy and add‐on regimes for treatment of chronic hepatitis B virus (HBV) infection may induce the accumulation of viral resistance mutations in patients, reducing the options for ongoing viral suppression. The induction of antiviral resistance by serial application of polymerase inhibitors does not necessarily imply that the subsequent combined use of the drugs will fail. Some HIV strains resistant to one polymerase inhibitor show increased susceptibility to another polymerase inhibitor. After failure of sequential lamivudine and adefovir monotherapy, two patients with hepatitis B changed to treatment with lamivudine plus adefovir and had renewed suppression of HBV. To study the mutational history of resistant HBV subpopulations in the two patients, a part of the HBV polymerase gene was amplified, cloned, sequenced, and analyzed for the presence of mutations, in sequential plasma samples. In both patients serial monotherapy caused the replacement in all HBV clones of wild‐type virus by classical lamivudine resistant mutants (L180M and M204V/I), which were replaced subsequently by adefovir resistant mutants (A181V and N236T). When finally lamivudine was added to adefovir, the A181V adefovir mutation persisted in all clones and lamivudine‐related mutations did not reappear. During 18 months of combination therapy, HBV‐DNA levels decreased 10,000, respectively, 1,000‐fold, despite the earlier resistance to lamivudine and adefovir. Although clinically insufficient, this effect indicates that HBV polymerase resistance mutations may be antagonistic, which is relevant if chronic HBV infection is to be treated by a combination of polymerase inhibitors. J. Med. Virol. 81:413–416, 2009. © 2009 Wiley‐Liss, Inc.
Association of lamivudine‐resistant mutational patterns with the antiviral effect of adefovir in patients with chronic hepatitis B
Authors: Cha Choong Keun , Kwon Hyeok Choon , Cheong Jae Youn , Cho Sung Won , Hong Sun Pyo , Kim Soo‐Ok , Yoo Wang Don 
Published: January 2009

AbstractAdefovir has a potent antiviral activity as a rescue treatment against lamivudine‐resistant strains. The aim of this study was to assess the patterns of lamivudine‐resistant mutations and their influence on the virologic response to adefovir rescue therapy in patients with lamivudine‐resistant chronic hepatitis B. Sixty‐seven patients with lamivudine‐resistant chronic hepatitis B were treated with adefovir monotherapy. Baseline blood samples were analyzed for lamivudine‐resistant mutations via restriction fragment mass polymorphism. Virologic responses, ALT normalization and loss of HBeAg were assessed. Serum HBV DNA levels were measured using real‐time PCR at baseline and 24 weeks of adefovir therapy. Of the 67 patients with chronic hepatitis B, 65 patients (97%) had lamivudine‐resistant mutations in the YMDD motif [27 (41%) rtM204I, 22 (34%) rtM204V, and 16 (25%) rtM204I/V]. In addition to the YMDD mutations, the rtL180M, rtL80I, and rtV173L mutations were also present in 78%, 43%, and 11% of patients, respectively. The rtM204V mutation always accompanied rtL180M, and rtL80I was always observed in conjunction with rtM204I. Decrease in mean serum HBV did not differ between patients carrying the rtM204I versus rtM204V mutant at week 24 (−3.3 vs. −3.3 log10 copies/ml, respectively; P = 0.303). The presence of the rtL180M, rtL80I, and rtV173L did not significantly affect viral load reduction during adefovir administration. These results demonstrate that the rtL80I mutant is co‐selected with rtM204I as a compensatory mutation in the same manner as rtL180M with rtM204V, and that adefovir shows similar antiviral efficacy against all of the evaluated patterns of lamivudine‐resistant HBV mutations. J. Med. Virol. 81:417–424, 2009. © 2009 Wiley‐Liss, Inc.
Cell cycle perturbation in the hepatocytes of HCV core transgenic mice following common bile duct ligation is associated with enhanced p21 expression
Authors: Chang Ming‐Ling , Chen Tsung‐Hsing , Chang Ming‐Yu , Yeh Chau‐Ting 
Published: January 2009

AbstractHepatitis C virus (HCV) core protein has been reported to alter the cell cycle in vitro, but the data remain inconclusive, and in vitro experiments do not represent precisely events that occur in vivo, which may involve hepatic inflammation or regeneration. A group of double‐transgenic mice carrying tetracycline transactivator (tTA) and HCV core that express conditionally the HCV core in the mature liver, and single‐transgenic mice carrying only tTA were subjected to sham laparotomy, 43% partial hepatectomy, or common bile duct ligation. The cell cycle markers, including cyclin A, B1, D, E1, Mcm‐2, phosphorylated histone 3 protein, Ki67, and p21Waf1/Cip1/Sdi1 (p21), were evaluated in liver samples obtained 3 days after the operation. No significant differences in the levels of any markers were observed between the double‐ and single‐transgenic mice following sham laparotomy. Among the mice that underwent common bile duct ligation, the double‐transgenic mice had lower levels of Ki67 (P = 0.0001), higher levels of cyclin D1 (P = 0.0001), and higher levels of p21 expression than the single‐transgenic mice. Among those that underwent partial hepatectomy, the double‐transgenic mice had higher p21 expression levels, but no significant differences in the levels of any other markers were observed between the double‐ and single‐transgenic mice. It is concluded that the HCV core alters the hepatocyte cell cycle in addition to inducing G1 arrest in vivo after common bile duct ligation, and is associated with enhanced p21 expression. This may account at least partially for the strong association between HCV‐related hepatocarcinogenesis and hepatic inflammation/ fibrosis. J. Med. Virol. 81:467–472, 2009. © 2009 Wiley‐Liss, Inc.
Interaction between human papillomavirus type 5 E2 and polo‐like kinase 1
Authors: Wang Wei‐Sheng , Lee Moon‐Sing , Tseng Chih‐En , Liao I‐Huan , Huang Shu‐Ping , Lin Ru‐Inn , Li Chin 
Published: January 2009

AbstractThe E2 protein of the papillomavirus plays an essential role in the viral life cycle. Through a yeast two‐hybrid screening, human polo‐like kinase 1 was found to interact with human papillomavirus type 5 E2. Further characterization identified that the domains responsible for the interaction are the transactivation domain of HPV‐5 E2 and the sequence between the kinase and the polo box domains of Plk1. In vivo, Plk1 and HPV‐5 E2 are colocalized at the nuclear speckles. In the skin epithelium not infected with epidermodysplasia verruciformis associated HPVs, Plk1 is expressed in the stratum basale, indicating that the Plk1–HPV‐5 E2 interaction likely occurs in the keratinocytes at the basal layer of the epithelium upon infection of HPV‐5. Both HPV‐5 E2 and Plk1 also interact with the E2 binding domain of Brd4. The E2 binding domain of Brd4 is phosphorylated by Plk1 in vitro, and this phosphorylation event is blocked by the presence of HPV‐5 E2. Hence, these findings suggest the possibility that the cellular function of Brd4 is de‐regulated by forming a complex with HPV‐5 E2 in the infected epithelial cells. J. Med. Virol. 81:536–544, 2009. © 2009 Wiley‐Liss, Inc.
Ultrasensitive assessment of residual HIV viraemia in HAART‐treated patients with persistently undetectable plasma HIV‐RNA: A cross‐sectional evaluation
Authors: Bonora Stefano , Nicastri Emanuele , Calcagno Andrea , Gonzalez de Requena Daniel , D'Ettorre Gabriella , Sarmati Loredana , Palmisano Lucia , Vullo Vincenzo , Di Perri Giovanni , Andreoni Massimo 
Published: January 2009

AbstractImprovements in HIV‐RNA assays have made accurate detection of as few as 2 copies/ml possible. This study objective was the evaluation of ultrasensitive HIV‐RNA quantitation (beneath current threshold: 50 copies/ml) in patients receiving different antiretroviral regimens. A cross‐sectional, ultrasensitive measurement of HIV‐RNA levels (detection limit: 2.5 HIV‐RNA copies/ml) was performed in 154 HIV‐1‐infected patients receiving ARV therapy, all classed as full responders according to the 50 copies/ml cut‐off. Patients were undergoing treatment with two nucleoside/nucleotide reverse transcriptase inhibitors (N/NtRTIs) plus nevirapine (NVP, n = 48), efavirenz (EFV, n = 57) or lopinavir/ritonavir (LPV/r, n = 49). Undetectable HIV‐RNA (<2.5 copies/ml) occurred in 29/48 (60.4%), 24/57 (42.1%) and 14/49 (28.6%) NVP, EFV and LPV/r recipients, respectively. Mean virological‐suppression (<50 copies/ml) duration was 28.6 months (median = 22, SD = 17.8), and only in LPV/r recipients length of suppression was associated with significantly lower HIV‐RNA levels (P = 0.015). Mean nadir CD4+ cell count of 270 cells/mm3 (median = 240, SD = 194.5) was significantly lower in the LPV/r arm (P < 0.001). Nadir CD4+ level correlated with virological suppression but had opposite trends between NVP (positive) and LPV/r (negative; two tailed P = 0.01). Logistic regression analysis showed NVP was the only independent factor associated with virologic suppression. NVP has demonstrated a distinct virological advantage at sub‐clinical viral loads, possibly due to its greater penetration in extra‐vascular compartments, warranting further investigation in the context of persistent low‐level viraemia in long‐term HAART. J. Med. Virol. 81:400–405, 2009. © 2009 Wiley‐Liss, Inc.
Mutations in the interferon sensitivity‐determining region of hepatitis C virus genotype 2a correlate with response to pegylated‐interferon‐alpha 2a monotherapy
Authors: Hayashi Kazuhiko , Katano Yoshiaki , Honda Takashi , Ishigami Masatoshi , Itoh Akihiro , Hirooka Yoshiki , Nakano Isao , Urano Fumihiro , Yoshioka Kentaro , Toyoda Hidenori , Kumada Takashi , Goto Hidemi 
Published: January 2009

AbstractThe interferon sensitivity‐determining region (ISDR) is thought to be inhibited by the double‐stranded RNA‐dependent protein kinase (PKR). Several studies have reported a relationship between the ISDR and interferon (IFN) responsiveness. However, this relationship is controversial. The aim of this study was to investigate whether genomic heterogeneity of the ISDR among patients with hepatitis C virus (HCV) genotype 2a affects the response to pegylated‐IFN‐alpha 2a monotherapy. Eighty patients (47 men, 33 women; mean age: 54.2 ± 12.9 years) infected with HCV genotype 2a were evaluated. HCV viral loads were determined by real‐time PCR. The ISDR (amino acids 2193–2228) was examined by direct sequencing. Thirty‐one patients received subcutaneous injections of pegylated‐IFN‐alpha 2a (180 µg) once weekly for 24 weeks, and 35 patients received injections for 48 weeks. Fourteen patients withdrew from treatment. Of the remaining 66 patients, 51 (77.3%) showed a sustained virologic response. Factors related to sustained virologic response on multivariate analysis were rapid virologic response (negative HCV at 4 weeks; odds ratio: 0.033; 95% confidence interval (95% CI) 0.003–0.363;P = 0.0052) and the number of mutations in the ISDR (odds ratio: 0.025; 95% CI 0.001–0.476;P = 0.0141). There were no significant differences in other factors, including sex, age, aspartate aminotransferase, alanine aminotransferase, platelet count, duration of treatment, and HCV viral load. Rapid virologic response and the ISDR sequence variations are significantly associated with response to pegylated‐IFN‐alpha 2a monotherapy in Japanese patients with HCV genotype 2a. J. Med. Virol. 81:459–466, 2009. © 2009 Wiley‐Liss, Inc.
Primary human endothelial cells support direct but not antibody‐dependent enhancement of dengue viral infection
Authors: Arévalo Maria T. , Simpson‐Haidaris Patricia J. , Kou Zhihua , Schlesinger Jacob J. , Jin Xia 
Published: January 2009

AbstractMicrovascular plasma leakage is the hallmark of dengue hemorrhagic fever and dengue shock syndrome. The precise molecular mechanisms leading to microvascular leakage are yet to be determined, but dengue virus (DENV) infection and consequent endothelial cell death has been suggested as its major cause. However, the extent of endothelial cell permissiveness to DENV infection and the magnitude of cell death following DENV infection are controversial. To clarify this issue, we analyzed the kinetics and consequences of DENV infection of human umbilical vein endothelial cells (HUVEC) using a novel molecularly cloned DENV2‐16681 virus. Viral replication was detected as early as 24 hr post‐infection by RT‐PCR and plaque assays. However, merely 2% of HUVEC were DENV antigen‐positive even after 96 hr of infection as measured by the FACS indirect immunofluorescence assays. Unlike monocytes/macrophages, HUVEC did not support antibody dependent enhancement of dengue viral infection due to a lack of FcγRI and FcγRII. Furthermore, DENV infection did not increase HUVEC apoptosis as compared to mock‐infected cells. Because in vitro only a small percentage of endothelial cells were productively infected in vitro with no significant apoptosis occurring in either infected or bystander cells, it would be important to re‐examine whether direct dengue viral infection of endothelium is the major cause of the extensive vascular leakage observed in patients with dengue hemorrhagic fever and dengue shock syndrome. J. Med. Virol. 81:519–528, 2009. © 2009 Wiley‐Liss, Inc.
Detection of human bocavirus in respiratory, fecal, and blood samples by real‐time PCR
Authors: Tozer Sarah J. , Lambert Stephen B. , Whiley David M. , Bialasiewicz Seweryn , Lyon Michael J. , Nissen Michael D. , Sloots Theo P. 
Published: January 2009

AbstractHuman bocavirus (HBoV) has been detected worldwide in respiratory samples. Two real‐time PCR assays, targeting the non‐structural protein (NP‐1) and viral protein (VP‐1) genes, were designed and validated to detect HBoV in patients with respiratory disease, gastroenteritis, or systemic illness. Sensitivity of the NP‐1 and VP‐1 assays were equal to the conventional PCR assay previously described by Allander et al. [2005: Proc Natl Acad Sci USA 102: 12891–12896] being 100%, and giving specificity of 94% and 93%, respectively. There was no cross‐reaction identified with unrelated respiratory agents, or to human DNA. The limits of detection were 10 copies of genomic DNA equivalents per reaction for both assays. The assays were used to screen three different sample populations, combined nose, and throat swabs (n = 96) from children with acute respiratory disease, fecal samples (n = 375) from adults, and children with gastroenteritis and whole blood (n = 229) collected from 31 immunocompromised children taken over an 18‐month period. In total 17 (18%) respiratory samples and 18 (4.8%) fecal samples were identified as having HBoV present. Of the pediatric whole blood specimens investigated, HBoV was detected in six (2.6%) samples from four patients. In summary, two real‐time PCR assays targeting different genes were designed and validated for use as screening methods for the detection of HBoV. HBoV was found in three different specimen types: parent‐collected combined nose–throat swabs, fecal samples collected from symptomatic individuals and whole blood from immunocompromised children. J. Med. Virol. 81:488–493, 2009. © 2009 Wiley‐Liss, Inc.
Exceptional genetic variability of hepatitis B virus indicates that Rwanda is east of an emerging African genotype E/A1 divide
Authors: Hübschen Judith M. , Mugabo Jules , Peltier Cécile Alexandra , Karasi Jean‐Claude , Sausy Aurélie , Kirpach Pierre , Arendt Vic , Muller Claude P. 
Published: January 2009

AbstractIn Western Africa, hepatitis B virus (HBV) genotype E predominates throughout a vast crescent spanning from Senegal to Namibia and at least to the Central African Republic to the East. Although from most of the eastern parts of sub‐Saharan Africa only limited sets of strains have been characterized, these belong predominantly to genotype A. To study how far the genotype E crescent extends to the East, a larger number of HBV strains from Rwanda were analyzed. Phylogenetic analysis of 45 S fragment sequences revealed strains of genotypes A (n = 30), D (n = 10), C (n = 4), and B (n = 1). Twelve genotype A sequences formed a new cluster clearly separated from the reference strains of the known sub‐genotypes. Thus, with four genotypes and at least six sub‐genotypes and a new cluster of genotype A strains, HBV shows an exceptional genetic variability in this small country, unprecedented in sub‐Saharan Africa. Despite this exceptional genetic variability, not a single genotype E virus was found indicating that this country does not belong to the genotype E crescent, but is east of an emerging African genotype E/A1 divide. J. Med. Virol. 81:435–440, 2009. © 2009 Wiley‐Liss, Inc.
An improved approach to identify epidemiological and phylogenetic transmission pairs of source and contact tracing of hepatitis B
Authors: Veldhuijzen Irene K. , Mes Ted H.M. , Mostert Maria C. , Niesters Hubert G.M. , Pas Suzan D. , Voermans Jolanda , de Man Robert A. , Götz Hannelore M. , van Doornum Gerard J.J. , Richardus Jan Hendrik 
Published: January 2009

AbstractThe transmission of infectious diseases can be traced using epidemiological and molecular information. In the current study, the congruence was assessed between sequence data of the hepatitis B virus (HBV) and epidemiological information resulting from source and contact tracing of patients seen at the Municipal Public Health Service in Rotterdam between 2002 and 2005. HBV genotypes A‐G were present in 62 acute and 334 chronic HBV patients. At the sequence level, the identical sequences of members of epidemiological transmission pairs and the rarity of such pairs provided strong support for correctness of the hypothesized transmission routes. The molecular support for epidemiological transmission pairs derived from source and contact tracing was further assessed by using topological constraints in parsimony analyses in agreement with epidemiological information, and by taking the presence of polymorphic sites of HBV within patients into account. This, in principle, allows mutations in epidemiological clusters. Of 22 epidemiological clusters, six could be refuted, four clusters received support from the molecular analysis, and support for the remaining twelve clusters was ambiguous. Two of the four epidemiological pairs that received molecular support had diverged (by 3 and 15 mutations). These results show that levels of divergence cannot be used simply as an indicator of the likelihood that groups of sequences constitute transmission pairs. Instead, to confirm or refute transmission pairs, it is necessary to assess the likelihood of a common origin of HBV variants in epidemiologically defined transmission groups relative to the HBV diversity in the local community. J. Med. Virol. 81:425–434, 2009. © 2009 Wiley‐Liss, Inc.