bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor targeting of baculovirus displaying a lymphatic homing peptide
Authors: Mäkelä Anna R. , Enbäck Juulia , Laakkonen Johanna P. , Vihinen‐Ranta Maija , Laakkonen Pirjo , Oker‐Blom Christian 
Published: July 2008

AbstractBackgroundTumor‐associated cells and vasculature express attractive molecular markers for site‐specific vector targeting. To attain tumor‐selective tropism, we recently developed a baculovirus vector displaying the lymphatic homing peptide LyP‐1, originally identified by ex vivo/in vivo screening of phage display libraries, on the viral envelope by fusion to the transmembrane anchor of vesicular stomatitis virus G‐protein.MethodsIn the present study, we explored the specificity and kinetics of viral binding and internalization as well as in vivo tumor homing of the LyP‐1 displaying virus to elucidate the applicability of baculovirus for targeted therapies.ResultsWe demonstrated that the LyP‐1 peptide contributes to saturable binding of baculovirus in human MDA‐MB‐435 and HepG2 carcinoma cells and escalates the kinetics of viral internalization leading to earlier nuclear accumulation and enhanced transgene expression. The LyP‐1 displaying virus also showed stronger competitiveness against transduction with wild‐type baculovirus, suggesting involvement of a specific receptor in cellular attachment and entry. Following intravenous injections, the modified virus accumulated within the human MDA‐MB‐435 and MDA‐MB‐231 carcinoma xenografts in mice with higher specificity and efficiency than the control virus. Targeting of the modified virus was more specific in the MDA‐MB‐435 than in the MDA‐MB‐231 xenografts as demonstrated by higher tumor accumulation and lower distribution in nontarget organs. No apparent cytotoxicity was associated with the surface modification.ConclusionsThis first demonstration of in vivo tumor targeting of a systemically administered, tropism‐modified baculoviral vector highlights the potential of baculovirus‐mediated targeted therapies. Copyright © 2008 John Wiley & Sons, Ltd.
Antibody‐mediated enhancement of the rate, magnitude, and responsiveness of vesicular stomatitis virus induced alpha interferon production
Authors: Green D.S. , Lum T. , Mullins B.T. , Green J.A. 
Published: July 2008

AbstractA majority of adults without evidence of exposure to vesicular stomatitis virus (VSV) have serum IgG antibodies that interact with pro‐inflammatory TLR7 in the presence of VSV, and enhance several aspects of VSV‐induced IFN‐α production. Enhancing IgG antibody enables human PBMC to make IFN‐α more rapidly and in higher titers in response to a broad range of VSV‐concentrations that include those too low to independently stimulate IFN‐α production. These antibody‐mediated functions compensate for the inherent delay in virus‐induced IFN‐α production in vitro, and have the potential to improve the in vivo IFN‐α response and effectively terminate infection before the occurence of clinically apparent disease. The frequent presence of enhancing antibody in persons without predictable VSV exposure has implications for naturally occurring infections with this and other viruses, and for the use of viruses as vaccine vectors and oncolytic agents. J. Med. Virol. 80:1675–1683, 2008. © 2008 Wiley‐Liss, Inc.
Human papillomavirus type 16 variants in cervical cancer from an admixtured population in Brazil
Authors: Junes‐Gill Katiana , Sichero Laura , Maciag Paulo Cesar , Mello Wyller , Noronha Vânia , Villa Luisa Lina 
Published: July 2008

AbstractSeveral studies indicate that molecular variants of HPV‐16 have different geographic distribution and risk associated with persistent infection and development of high‐grade cervical lesions. In the present study, the frequency of HPV‐16 variants was determined in 81 biopsies from women with cervical intraepithelial neoplasia grade III or invasive cervical cancer from the city of Belem, Northern Brazil. Host DNAs were also genotyped in order to analyze the ethnicity‐related distribution of these variants. Nine different HPV‐16 LCR variants belonging to four phylogenetic branches were identified. Among these, two new isolates were characterized. The most prevalent HPV‐16 variant detected was the Asian‐American B‐2, followed by the European B‐12 and the European prototype. Infections by multiple variants were observed in both invasive cervical cancer and cervical intraepithelial neoplasia grade III cases. The analysis of a specific polymorphism within the E6 viral gene was performed in a subset of 76 isolates. The E6‐350G polymorphism was significantly more frequent in Asian‐American variants. The HPV‐16 variability detected followed the same pattern of the genetic ancestry observed in Northern Brazil, with European, Amerindian and African roots. Although African ancestry was higher among women infected by the prototype, no correlation between ethnical origin and HPV‐16 variants was found. These results corroborate previous data showing a high frequency of Asian‐American variants in cervical neoplasia among women with multiethnic origin. J. Med. Virol. 80:1639–1645, 2008. © 2008 Wiley‐Liss, Inc.
Diagnosis and clinical impact of occult hepatitis B infection in patients with biopsy proven chronic hepatitis C: A multicenter study
Authors: Evangelista Sagnelli , Michele Imparato , Nicola Coppola , Raffaella Pisapia , Caterina Sagnelli , Vincenzo Messina , Guido Piai , Maria Stanzione , Marika Bruno , Giovanni Moggio , Nunzio Caprio , Giuseppe Pasquale , Camillo Del Vecchio Blanco 
Published: July 2008

AbstractOccult hepatitis B virus (HBV) infection in patients with chronic hepatitis C has been found associated with severe liver damage, low response to interferon treatment and increased risk of developing HCC. However, doubts remain on its clinical impact and the sensitivity and specificity of its detection. HBV‐DNA was sought by PCR in plasma, peripheral blood mononuclear cells (PBMCs) and liver compartments of 89 patients with biopsy proven chronic hepatitis C, using sets of primers for core (“c”), surface (“s”), and x (“x”) regions of HBV genome. Occult HBV infection was defined by the presence of HBV‐DNA in at least two different PCRs in at least one compartment. Occult HBV infection was detected in 37 (41.6%) of the 89 patients investigated. It was more frequent (80.8%) in 26 anti‐ HBs negative/anti‐HBc positive patients than in 18 anti‐HBs/anti‐HBc positive (61.1%, P < 0.01) and 45 anti‐HBs/anti‐HBc negative (11.1%, P < 0.0001), and more frequently in liver (91.9%) than in PBMCs (62.2%) and plasma (32.4%). No association was found between occult HBV infection and the degree of liver necroinflammation and fibrosis. However, considering the 52 patients without occult HBV infection, 51.4% of 35 patients with genotype 1 and 5.9% of 17 with genotype non‐1 showed severe fibrosis (P = 0.003); patients with occult HBV infection did not show such difference. Instead of seeking occult HBV infection in patients with chronic hepatitis C, both anti‐HBs negative/anti‐HBc positive and anti‐HBs positive/anti‐HBc positive, in plasma alone, more reliable information can also be obtained from the liver tissue and PBMCs. J. Med. Virol. 80:1547–1553, 2008. © 2008 Wiley‐Liss, Inc.
Genotypic analysis of two hypervariable human cytomegalovirus genes
Authors: Bradley Amanda J. , Kovács Ida J. , Gatherer Derek , Dargan Derrick J. , Alkharsah Khaled R. , Chan Paul K.S. , Carman William F. , Dedicoat Martin , Emery Vincent C. , Geddes Colin C. , Gerna Giuseppe , Ben‐Ismaeil Bassam , Kaye Steve , McGregor Alistair , Moss Paul A. , Pusztai Rozalia , Rawlinson William D. , Scott Gillian M. , Wilkinson Gavin W.G. , Schulz Thomas F. , Davison Andrew J. 
Published: July 2008

AbstractMost human cytomegalovirus (HCMV) genes are highly conserved in sequence among strains, but some exhibit a substantial degree of variation. Two of these genes are UL146, which encodes a CXC chemokine, and UL139, which is predicted to encode a membrane glycoprotein. The sequences of these genes were determined from a collection of 184 HCMV samples obtained from Africa, Australia, Asia, Europe, and North America. UL146 is hypervariable throughout, whereas variation in UL139 is concentrated in a sequence encoding a potentially highly glycosylated region. The UL146 sequences fell into 14 genotypes, as did all previously reported sequences. The UL139 sequences grouped into 8 genotypes, and all previously reported sequences fell into a subset of these. There were minor differences among continents in genotypic frequencies for UL146 and UL139, but no clear geographical separation, and identical nucleotide sequences were represented among communities distant from each other. The frequent detection of multiple genotypes indicated that mixed infections are common. For both genes, the degree of divergence was sufficient to preclude reliable sequence alignments between genotypes in the most variable regions, and the mode of evolution involved in generating the genotypes could not be discerned. Within genotypes, constraint appears to have been the predominant mode, and positive selection was detected marginally at best. No evidence was found for linkage disequilibrium. The emerging scenario is that the HCMV genotypes developed in early human populations (or even earlier), becoming established via founder or bottleneck effects, and have spread, recombined and mixed worldwide in more recent times. J. Med. Virol. 80:1615–1623, 2008. © 2008 Wiley‐Liss, Inc.
Epidemiologic characteristics and seasonal distribution of human metapneumovirus infections in five epidemic seasons in Stockholm, Sweden, 2002–2006
Authors: Rafiefard Farideh , Yun ZhiBing , Örvell Claes 
Published: July 2008

AbstractThe presence of human metapneumovirus (hMPV) was analyzed retrospectively by reverse transcriptase‐polymerase chain reaction (RT‐PCR) in five epidemic seasons, in Stockholm, 2002–2006. The occurrence of hMPV was compared with five common respiratory viruses; respiratory syncytial virus, influenza A virus, influenza B virus, parainfluenza virus and adenovirus. With a detection rate of 2.9% (n = 143/4,989) in nasopharyngeal samples over the whole period, hMPV was the fourth most common respiratory virus after RSV, influenza A and parainfluenza virus. hMPV genotype A dominated over genotype B, out of 91 genotyped virus samples 87 belonged to genotype A and four belonged to genotype B. Approximately 50.3% (n = 72/143) of the hMPV positive patients were <3 years, 49.7% (71/143) were ≥3 years and 38,5% (n = 55/143) were <1 year. The relative frequencies of hMPV infections in the three age groups were 2.8% (72/2,579), 2.9% (71/2,410) and 2.6% (55/2,122), respectively. This age distribution differed from RSV, influenza A, B and parainfluenza virus. hMPV epidemics peaked in March, not coincident with RSV or parainfluenza virus. In successive epidemic seasons, large outbreaks of hMPV alternated with small outbreaks in a regular, biannual pattern. Large hMPV virus epidemics were anticyclical to large RSV epidemics. It is concluded that the epidemiology of hMPV differs markedly from other common respiratory viruses. J. Med. Virol. 80:1631–1638, 2008. © 2008 Wiley‐Liss, Inc.
Reliable detection and quantitation of viral nucleic acids in oral fluid: Liquid phase‐based sample collection in conjunction with automated and standardized molecular assays
Authors: Raggam Reinhard B. , Wagner Jasmin , Michelin Birgit D. A. , Putz‐Bankuti Csilla , Lackner Andreas , Bozic Michael , Stauber Rudolf E. , Santner Brigitte I. , Marth Egon , Kessler Harald H. 
Published: July 2008

AbstractOral fluid has been used widely as sample matrix for the detection and quantitation of viral nucleic acids. However, in the vast majority of previous studies, various methods for collection of oral fluid and molecular assays lacking automation and standardization were used. In this study, a new standardized liquid phase‐based saliva collection system was employed followed by a fully automated viral nucleic acid extraction and real‐time PCR using commercially available in vitro diagnostics (IVD)/Conformité Européene (CE) labeled molecular assays. When the lower limit of detection of herpes simplex virus (HSV)‐1/2 DNA, varicella zoster virus (VZV) DNA, and hepatitis C virus (HCV) RNA in spiked oral fluid was tested, the results were found to be comparable to those with defined sample materials recommended by the assay manufacturers. When clinical specimens were investigated, 21 of 25 (84%) oral fluids obtained from patients with clinically apparent herpetic lesions tested positive for HSV DNA, 7 of 10 (70%) oral fluids obtained from patients with Ramsay Hunt Syndrome tested positive for VZV DNA, and 19 of 40 (48%) oral fluids collected from patients with chronic HCV infection tested positive for HCV RNA. The automated extraction instruments completed all extractions without malfunction and no inhibitions were observed throughout the entire study. Liquid phase‐based saliva collection in conjunction with automated and standardized commercially available molecular assays allows reliable quantitation of viral nucleic acids in oral fluid samples and may contribute to improved comparable and interpretable test results. J. Med. Virol. 80:1684–1688, 2008. © 2008 Wiley‐Liss, Inc.
Genetic variability in the G protein gene of human respiratory syncytial virus isolated from the Campinas metropolitan region, Brazil
Authors: Antoniassi da Silva Luciana Helena , Spilki Fernando Rosado , Riccetto Adriana Gut Lopes , de Almeida Renata Servan , Baracat Emílio Carlos Elias , Arns Clarice Weis 
Published: July 2008

AbstractHuman respiratory syncytial virus (hRSV) is recognized as the most important viral agent of serious respiratory tract diseases in the pediatric population worldwide. A prospective study for hRSV was conducted in children ageing less than 1 year admitted in two university hospitals in Campinas, São Paulo, Brazil. The aim of the present study was to investigate the genetic variability of both A and B subgroups of hRSV isolated during an epidemic period in the Campinas metropolitan region, Brazil, by sequencing a variable region of the G protein gene. Phylogenetic trees were constructed from alignments of sequences available in the GenBank database and Brazil isolates for hRSV A and B. The data demonstrate that Brazilian isolates clusters together with A and B viruses from Kenya, New Zealand, South Africa, West Virginia, United States (CH, Rochester), and other Brazilian isolates. Phylogenetic analysis of subgroup A isolates showed that the sequences obtained on the present study falls on three clusters, namely GA2, GA5, and SAA1 that co‐circulate during the analyzed period. Subgroup B isolates detected belongs to three genotypes, GB3 (SAB3) and BA (BAIII). Different subgroup B genotypes were detected and BA isolates present in our samples showed some degree of genetic variability. This is one of the first reports on the molecular epidemiology of hRSV strains from the Campinas metropolitan region, São Paulo state, Brazil. And is also the first description of the circulation pattern of hRSV genotypes in two university hospitals, revealing interesting differences between the two subgroups of the virus. J. Med. Virol. 80:1653–1660, 2008. © 2008 Wiley‐Liss, Inc.
High prevalence of hepatitis C virus infection and predominance of genotype 4 in rural gabon
Authors: Ndong‐Atome G.R. , Makuwa M. , Ouwe‐Missi‐Oukem‐Boyer O. , Pybus O.G. , Branger M. , Le Hello S. , Boye‐Cheik S.B. , Brun‐Vezinet F. , Kazanji M. , Roques P. , Bisser S. 
Published: July 2008

AbstractHepatitis C (HCV) molecular epidemiology is documented poorly in central African countries. In response to this, a population‐based study of 319 consenting adults resident in a remote village of Gabon was undertaken (mean age: 38 years; age range: 13–85+; sex ratio: 0.74). Screening for anti‐HCV antibodies was performed using ELISA and recombinant immunoblot assay. Seropositive samples were assessed further with viral load and genotyping techniques. Sixty‐six (20.7%) individuals were HCV seropositive. Viral loads ranged from 600 to 24.9 million IU/ml (median: 372,500). Seroprevalence and viral loads increased significantly with age (P < 10−5 and P < 0.003, respectively). HCV sequences of the 5′UTR genome region were obtained from 60 (90.9%) samples and NS5B region sequences were obtained from 22 (36.6%) samples. All strains belonged to subtypes of genotype 4: 4e (72.7%), 4c (13.6%), 4p (4.5%), 4r (4.5%) and one unclassified genotype 4 strain. Evolutionary analysis of the subtype 4e sequences indicates a period of raised transmission during the early twentieth century. J. Med. Virol. 80:1581–1587, 2008. © 2008 Wiley‐Liss, Inc.
Weight affect relapse rates in latinos with genotype 2/3 chronic hepatitis C (CHC) treated with peg IFN alfa‐2a (Pegasys) 180 mcg/week and 800 mg daily of ribavirin for 24 weeks
Authors: Rodríguez‐Torres Maribel , Ríos‐Bedoya Carlos F. , Ortiz‐Lasanta Grisell , Purcell‐Arevalo Dagmary , Marxuach‐Cuétara Acisclo , Jiménez‐Rivera Josselyn 
Published: July 2008

AbstractEfficacy of chronic hepatitis C (CHC) treatment with Peg‐IFN and Ribavirin (RBV) is superior for genotypes 2/3 (GT‐2/3) than for genotype 1 (GT‐1) patients. Efficacy of treatment in Latinos infected with GT‐2/3 is unknown. The purpose of the study was to examine efficacy of Peg‐IFN/RBV in Latinos and factors that predict sustained viral response (SVR). This was a retrospective study of GT‐2/3 patients treated with Peg‐IFN alfa‐2a and RBV for 24 weeks. Multiple baseline characteristics were evaluated. SVR and relapse rates were calculated, as well as multiple regression models performed to examine factors that predict SVR and relapse, as genotype, HVL, weight, steatosis at liver biopsy, total cholesterol triglyceride and diabetes. Thirty five consecutive patients were included in the study; [26] GT‐2 and [9] GT‐3. Baseline characteristics were similar between both genotypes. SVR was (18/26) or 69.2% for GT‐2 and (8/9) or 88.9% for GT‐3 for combined SVR of (26/35), 74.3%. Relapse rates were 28.0% for GT‐2 and 11.1% for GT‐3 patients for a combined relapse rate of 23.5%. Patients heavier than 75 kg had relapse rates twofold higher than leaner patients, (6/21) or 28.6% versus (2/14) or 14.3% (P = 0.088). Weight increase in kg was the only predictor for risk of relapse, P = 0.043 (SD 0.0445 95% CI 1.0026–1.1772). In conclusion, Latinos heavier than 75 kg with GT‐2/3 HCV infection achieve lower SVR than those who weight less than 75 kg, because a higher relapse rate. More research in ethnic and racial minorities is needed to further establish optimal treatment in this population. J. Med. Virol. 80:1576–1580, 2008. © 2008 Wiley‐Liss, Inc.
Characterization of influenza A/Fujian/411/2002(H3N2)‐like viruses isolated in Portugal between 2003 and 2005
Authors: Pechirra Pedro , Gonçalves Paulo , Arraiolos Ana , Coelho Anabela , Rebelo‐de‐Andrade Helena 
Published: July 2008

AbstractIn Portugal, influenza surveillance is achieved through the National Influenza Surveillance Programme (NISP), in close collaboration with other European and global surveillance networks. The NISP integrates epidemiological, clinical and virological data based on the information collected by a Network of Sentinel Medical Practitioners and by a network of Emergency Units of Hospitals and Health Care Centres. In this study, genetic and antigenic characterization of influenza A viruses of the A/Fujian/411/2002 lineage, isolated during the 2003/2004 and 2004/2005 influenza winter seasons, in the context of the NISP, are described. Antigenic analysis of A/Fujian/411/2002‐like viruses, first detected and isolated during the 2003/2004 winter season, revealed a close similarity with the reference strains A/Kumamoto/102/2002 and A/Wyoming/3/2003. Genetic analysis confirmed this similarity and revealed two different phylogenetic branches. The 2004/2005 influenza A(H3) isolates formed, both antigenic and genetically, a more homogeneous group and were closely related to A/Oslo/807/2004 and A/California/7/2004. During this season, the characterization of the influenza viral strains has shown continuous evolution to variants close related to A/Oslo/807/2004. The majority of amino acid substitutions detected in the haemagglutinin occurred at antigenic sites. This study reflects the contribution of individual countries for the surveillance and knowledge of the molecular epidemiology of the infection, essential for a concerted action towards the global monitoring of the disease. It also reflects the importance of constant monitoring of genetic and antigenic characteristics of circulating influenza strains, which will certainly be a major contribution to the formulation of influenza vaccines. J. Med. Virol. 80:1624–1630, 2008. © 2008 Wiley‐Liss, Inc.
Hepatitis C virus seropositivity in a South African Cohort of HIV co‐infected, ARV naïve patients is associated with renal insufficiency and increased mortality
Authors: Parboosing Raveen , Paruk Imran , Lalloo Umesh G. 
Published: July 2008

AbstractHIV is known to affect the epidemiology, transmission, pathogenesis and natural history of HCV infection whilst studies on the effects of HCV on HIV have shown conflicting results and are confounded by the influence of intravenous drug use and antiretroviral therapy. This study was conducted in KwaZulu‐Natal Province in South Africa where HIV is predominantly a sexually transmitted infection. Intravenous drug use is rare in this region and the study population was naïve to antiretroviral therapy. For this study, specimens from selected sentinel sites submitted to a central laboratory for routine HIV testing were screened for anti‐HCV IgG antibodies. HIV positive HCV‐positive patients were compared to HIV‐positive HCV‐negative patients in a subgroup of patients within this cohort in order to determine if HCV sero‐prevalence was associated with clinical outcomes in a linked anonymous retrospective chart survey. The prevalence of HCV was 6.4% and that of HIV, 40.2% (n = 1,937). There was a significantly higher prevalence of HCV among HIV infected patients as compared to HIV negative patients (13.4% vs. 1.73% respectively) (n = 1,937, P < 0.001). HCV‐HIV co‐infected patients had significantly increased mortality (8.3 vs. 21%) (n = 162, P < 0.02). A significant association was found between HCV serostatus and abnormal urea levels (15.4 vs. 7.3 mmol/L, n = 134, P < 0.001) and creatinine levels (252.2 vs. 144.4 µmol/L, n = 134, P < 0.01). This study has found that hepatitis C co‐infection is more common in HIV positive individuals and is associated with an increased mortality and renal morbidity. J. Med. Virol. 80:1530–1536, 2008. © 2008 Wiley‐Liss, Inc.
Evaluation of E1A double mutant oncolytic adenovectors in anti‐glioma gene therapy
Authors: Ulasov Ilya V. , Tyler Matthew A. , Rivera Angel A. , Nettlebeck Dirk M. , Douglas Joanne T. , Lesniak Maciej S. 
Published: July 2008

AbstractMalignant glioma, in particular glioblastoma multiforme (GBM), represents one of the most devastating cancers currently known and existing treatment regimens do little to change patient prognosis. Conditionally replicating adenoviral vectors (CRAds) represent attractive experimental anti‐cancer agents with potential for clinical application. However, early protein products of the wild type adenovirus backbone—such as E1A—limit CRAds' replicative specificity. In this study, we evaluated the oncolytic potency and specificity of CRAds in which p300/CPB and/or pRb binding capacities of E1A were ablated to reduce non‐specific replicative cytolysis. In vitro cytopathic assays, quantitative PCR analysis, Western blot, and flow cytometry studies demonstrate the superior anti‐glioma efficacy of a double‐mutated CRAd, Ad2/24CMV, which harbors mutations that reduce E1A binding to p300/CPB and pRb. When compared to its single‐mutated and wild type counterparts, Ad2/24CMV demonstrated attenuated replication and cytotoxicity in representative normal human brain while displaying enhanced replicative cytotoxicity in malignant glioma. These results have implications for the development of double‐mutated CRAd vectors for enhanced GBM therapy. J. Med. Virol. 80:1595–1603, 2008. © 2008 Wiley‐Liss, Inc.