bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidemiology and Genetic Characterization of Hepatitis A Virus Genotype IIA
Authors: Desbois Delphine , Couturier Elisabeth , Mackiewicz Vincent , Graube Arielle , Letort Marie-José , Dussaix Elisabeth , Roque-Afonso Anne-Marie 
Published: July 2010

ABSTRACT
Three hepatitis A virus (HAV) genotypes, I, II, and III, divided into subtypes A and B, infect humans. Genotype I is the most frequently reported, while genotype II is hardly ever isolated, and its genetic diversity is unknown. From 2002 to 2007, a French epidemiological survey of HAV identified 6 IIA isolates, mostly from patients who did not travel abroad. The possible African origin of IIA strains was investigated by screening the 2008 mandatory notification records of HAV infection: 171 HAV strains from travelers to West Africa and Morocco were identified. Genotyping was performed by sequencing of the VP1/2A junction in 68 available sera. Entire P1 and 5′ untranslated regions of IIA strains were compared to reference sequences of other genotypes. The screening retrieved 5 imported IIA isolates. An additional autochthonous case and 2 more African cases were identified in 2008 and 2009, respectively. A total of 14 IIA isolates (8 African and 6 autochthonous) were analyzed. IIA sequences presented lower nucleotide and amino acid variability than other genotypes. The highest variability was observed in the N-terminal region of VP1, while for other genotypes the highest variability was observed at the VP1/2A junction. Phylogenetic analysis identified 2 clusters, one gathering all African and two autochthonous cases and a second including only autochthonous isolates. In conclusion, most IIA strains isolated in France are imported by travelers returning from West Africa. However, the unexplained contamination mode of autochthonous cases suggests another, still to be discovered geographical origin or a French reservoir to be explored.
Leukoencephalopathy Associated with Parvovirus Infection in Cretan Hound Puppies
Authors: Schaudien D. , Polizopoulou Z. , Koutinas A. , Schwab S. , Porombka D. , Baumgärtner W. , Herden C. 
Published: July 2010

ABSTRACTLeukoencephalopathies in dogs encompass presumably inherited conditions such as leukodystrophies, hypomyelination or spongiform degeneration, but other causes, such as virus infections and toxic or nutritional factors, might also play a contributory role. In this report, we provide evidence of parvovirus infection and replication in the brains of five 6-week-old Cretan hound puppies suffering from a puppy shaker syndrome and leukoencephalopathy. Although these puppies belonged to two different litters, they were closely related, tracing back two generations to the same sire. Histologically, a mild to moderate lymphohistiocytic meningitis, with focal lymphohistiocytic leukoencephalitis in two animals, and a mild to moderate vacuolation with myelin loss, mainly in the white matter of the cerebellum was detected. Vacuolation was also found in the corpus callosum, fimbria hippocampi, mesencephalon, capsula interna, basal ganglia, and hypothalamus. By immunohistology andin situhybridization, either parvoviral antigen, DNA, mRNA, or replicative intermediate DNA were detected in the cerebellum, hippocampus, periventricular areas, corpus callosum, cerebral cortex, medulla oblongata, and spinal cord. Parvovirus antigen, DNA, and mRNA were present in cells of the outer granular layer of the cerebellum and in periventricular cells, most likely representing spongioblasts, glial cells, neurons, endothelial cells, occasional macrophages, and ependymal cells. Sequencing revealed canine parvovirus type 2 stretches. Thus, an association of parvovirus infection with the leukoencephalopathy seems likely, possibly facilitated by a genetic predisposition due to the mode of inbreeding in this particular dog breed.
Induction and Inhibition of Type I Interferon Responses by Distinct Components of Lymphocytic Choriomeningitis Virus
Authors: Zhou Shenghua , Cerny Anna M. , Zacharia An , Fitzgerald Katherine A. , Kurt-Jones Evelyn A. , Finberg Robert W. 
Published: July 2010

ABSTRACTType I interferons (IFNs) play a critical role in the host defense against viruses. Lymphocytic choriomeningitis virus (LCMV) infection induces robust type I IFN production in its natural host, the mouse. However, the mechanisms underlying the induction of type I IFNs in response to LCMV infection have not yet been clearly defined. In the present study, we demonstrate that IRF7 is required for both the early phase (day 1 postinfection) and the late phase (day 2 postinfection) of the type I IFN response to LCMV, and melanoma differentiation-associated gene 5 (MDA5)/mitochondrial antiviral signaling protein (MAVS) signaling is crucial for the late phase of the type I IFN response to LCMV. We further demonstrate that LCMV genomic RNA itself (without other LCMV components) is able to induce type I IFN responses in various cell types by activation of the RNA helicases retinoic acid-inducible gene I (RIG-I) and MDA5. We also show that expression of the LCMV nucleoprotein (NP) inhibits the type I IFN response induced by LCMV RNA and other RIG-I/MDA5 ligands. These virus-host interactions may play important roles in the pathogeneses of LCMV and other human arenavirus diseases.
Prophylactic Treatment with a G Glycoprotein Monoclonal Antibody Reduces Pulmonary Inflammation in Respiratory Syncytial Virus (RSV)-Challenged Naïve and Formalin-Inactivated RSV-Immunized BALB/c Mice
Authors: Radu Gertrud U. , Caidi Hayat , Miao Congrong , Tripp Ralph A. , Anderson Larry J. , Haynes Lia M. 
Published: July 2010

ABSTRACT

We examined whether prophylactically administered anti-respiratory syncytial virus (anti-RSV) G monoclonal antibody (MAb) would decrease the pulmonary inflammation associated with primary RSV infection and formalin-inactivated RSV (FI-RSV)-enhanced disease in mice. MAb 131-2G administration 1 day prior to primary infection reduced the pulmonary inflammatory response and the level of RSV replication. Further, intact or F(ab′)
2
forms of MAb 131-2G administered 1 day prior to infection in FI-RSV-vaccinated mice reduced enhanced inflammation and disease. This study shows that an anti-RSV G protein MAb might provide prophylaxis against both primary infection and FI-RSV-associated enhanced disease. It is possible that antibodies with similar reactivities might prevent enhanced disease and improve the safety of nonlive virus vaccines.
RNA 5′-Triphosphatase Activity of the Hepatitis E Virus Helicase Domain
Authors: Karpe Yogesh A. , Lole Kavita S. 
Published: July 2010

ABSTRACT

Hepatitis E virus (HEV) has a positive-sense RNA genome with a 5′-m7G cap. HEV open reading frame 1 (ORF1) encodes a polyprotein with multiple enzyme domains required for replication. HEV helicase is a nucleoside triphosphatase (NTPase) with the ability to unwind RNA duplexes in the 5′-to-3′ direction. When incubated with 5′-[γ-
32
P]RNA and 5′-[α-
32
P]RNA, HEV helicase released
32
P only from 5′-[γ-
32
P]RNA, showing specificity for the γ-β-triphosphate bond. Removal of γ-phosphate from the 5′ end of the primary transcripts (pppRNA to ppRNA) by RNA triphosphatase is an essential step during cap formation. It is suggested that HEV employs the helicase to mediate the first step of 5′ cap synthesis.
Dendritic Cells Loaded with Tumor B Cells Elicit Broad Immunity against Murine Gammaherpesvirus 68 but Fail To Prevent Long-Term Latency
Authors: Weslow-Schmidt Janet , Ye Fang , Cush Stephanie S. , Stuller Kathleen A. , Blackman Marcia A. , Flaño Emilio 
Published: July 2010

ABSTRACT
It is still unknown whether a noninfectious gammaherpesvirus vaccine is able to prevent or reduce virus persistence. This led us to use dendritic cells loaded with tumor B cells as a vaccine approach for the murine gammaherpesvirus 68 (γHV68) model of infection. Dendritic cells loaded with UV-irradiated latently infected tumor B cells induce broad, strong, and long-lasting immunity against γHV68. Dendritic cell vaccination prevents the enlargement of lymph nodes and severely limits acute infection and early latency but does not prevent γHV68 from establishing long-term latency. Our findings support the concept that attenuated viruses may be the best vaccine option for preventing gammaherpesvirus persistence.
Mutational Mapping of UL130 of Human Cytomegalovirus Defines Peptide Motifs within the C-Terminal Third as Essential for Endothelial Cell Infection
Authors: Schuessler Andrea , Sampaio Kerstin Laib , Scrivano Laura , Sinzger Christian 
Published: July 2010

ABSTRACT
The UL130 gene is one of the major determinants of endothelial cell (EC) tropism of human cytomegalovirus (HCMV). In order to define functionally important peptides within this protein, we have performed a charge-cluster-to-alanine (CCTA) mutational scanning of UL130 in the genetic background of a bacterial artificial chromosome-cloned endotheliotropic HCMV strain. A total of 10 charge clusters were defined, and in each of them two or three charged amino acids were replaced with alanines. While the six N-terminal clusters were phenotypically irrelevant, mutation of the four C-terminal clusters each caused a reduction of EC tropism. The importance of this protein domain was further emphasized by the fact that the C-terminal pentapeptide PNLIV was essential for infection of ECs, and the cell tropism could not be rescued by a scrambled version of this sequence. We conclude that the C terminus of the UL130 protein serves an important function for infection of ECs by HCMV. This makes UL130 a promising molecular target for antiviral strategies, e.g., the development of antiviral peptides.
Inhibition of Cellular Proteasome Activities Mediates HBX-Independent Hepatitis B Virus ReplicationIn Vivo
Authors: Zhang Zhensheng , Sun Eun , Ou Jing-hsiung James , Liang T. Jake 
Published: July 2010

ABSTRACTThe X protein (HBX) of the hepatitis B virus (HBV) is essential for HBV productive infectionin vivo. Our previous study (Z. Hu, Z. Zhang, E. Doo, O. Coux, A. L. Goldberg, and T. J. Liang, J. Virol. 73:7231-7240, 1999) shows that interaction of HBX with the proteasome complex may underlie the pleiotropic functions of HBX. Previously, we demonstrated that HBX affects hepadnaviral replication through a proteasome-dependent pathway in cell culture models. In the present study, we studied the effect of the proteasome inhibitor MLN-273 in two HBV mouse models. We demonstrated that administration of MLN-273 to transgenic mice containing the replication-competent HBV genome with the defective HBX gene substantially enhanced HBV replication, while the compound had a minor effect on wild-type HBV transgenic mice. Similar results were obtained by using C57BL/6 mice infected with recombinant adenoviruses expressing the replicating HBV genome. Our data suggest that HBV replication is subjected to regulation by cellular proteasome and HBX functions through the inhibition of proteasome activities to enhance HBV replicationin vivo.
Foot-and-Mouth Disease Virus Replicates Only Transiently in Well-Differentiated Porcine Nasal Epithelial Cells
Authors: Dash Pradyot , Barnett Paul V. , Denyer Michael S. , Jackson Terry , Stirling Catrina M. A. , Hawes Philippa C. , Simpson Jennifer L. , Monaghan Paul , Takamatsu Haru-H. 
Published: July 2010

ABSTRACTThree-dimensional (3D) porcine nasal mucosal and tracheal mucosal epithelial cell cultures were developed to analyze foot-and-mouth disease virus (FMDV) interactions with mucosal epithelial cells. The cells in these cultures differentiated and polarized until they closely resemble the epithelial layers seenin vivo. FMDV infected these cultures predominantly from the apical side, primarily by binding to integrin αvβ6, in an Arg-Gly-Asp (RGD)-dependent manner. However, FMDV replicated only transiently without any visible cytopathic effect (CPE), and infectious progeny virus could be recovered only from the apical side. The infection induced the production of beta interferon (IFN-β) and the IFN-inducible gene Mx1 mRNA, which coincided with the disappearance of viral RNA and progeny virus. The induction of IFN-β mRNA correlated with the antiviral activity of the supernatants from both the apical and basolateral compartments. IFN-α mRNA was constitutively expressed in nasal mucosal epithelial cellsin vitroandin vivo. In addition, FMDV infection induced interleukin 8 (IL-8) protein, granulocyte-macrophage colony-stimulating factor (GM-CSF), and RANTES mRNA in the infected epithelial cells, suggesting that it plays an important role in modulating the immune response.
The Architecture and Chemical Stability of the Archaeal
Sulfolobus
Turreted Icosahedral Virus
Authors: Khayat Reza , Fu Chi-yu , Ortmann Alice C. , Young Mark J. , Johnson John E. 
Published: July 2010

ABSTRACT

Viruses utilize a diverse array of mechanisms to deliver their genomes into hosts. While great strides have been made in understanding the genome delivery of eukaryotic and prokaryotic viruses, little is known about archaeal virus genome delivery and the associated particle changes. The
Sulfolobus
turreted icosahedral virus (STIV) is a double-stranded DNA (dsDNA) archaeal virus that contains a host-derived membrane sandwiched between the genome and the proteinaceous capsid shell. Using cryo-electron microscopy (cryo-EM) and different biochemical treatments, we identified three viral morphologies that may correspond to biochemical disassembly states of STIV. One of these morphologies was subtly different from the previously published 27-Å-resolution electron density that was interpreted with the crystal structure of the major capsid protein (MCP). However, these particles could be analyzed at 12.5-Å resolution by cryo-EM. Comparing these two structures, we identified the location of multiple proteins forming the large turret-like appendages at the icosahedral vertices, observed heterogeneous glycosylation of the capsid shell, and identified mobile MCP C-terminal arms responsible for tethering and releasing the underlying viral membrane to and from the capsid shell. Collectively, our studies allow us to propose a fusogenic mechanism of genome delivery by STIV, in which the dismantled capsid shell allows for the fusion of the viral and host membranes and the internalization of the viral genome.
Structure and Function Analysis of Therapeutic Monoclonal Antibodies against Dengue Virus Type 2
Authors: Sukupolvi-Petty Soila , Austin S. Kyle , Engle Michael , Brien James D. , Dowd Kimberly A. , Williams Katherine L. , Johnson Syd , Rico-Hesse Rebeca , Harris Eva , Pierson Theodore C. , Fremont Daved H. , Diamond Michael S. 
Published: July 2010

ABSTRACT

Dengue virus (DENV) is the most prevalent insect-transmitted viral disease in humans globally, and currently no specific therapy or vaccine is available. Protection against DENV and other related flaviviruses is associated with the development of antibodies against the viral envelope (E) protein. Although prior studies have characterized the neutralizing activity of monoclonal antibodies (MAbs) against DENV type 2 (DENV-2), none have compared simultaneously the inhibitory activity against a genetically diverse range of strains
in vitro
, the protective capacity in animals, and the localization of epitopes. Here, with the goal of identifying MAbs that can serve as postexposure therapy, we investigated in detail the functional activity of a large panel of new anti-DENV-2 mouse MAbs. Binding sites were mapped by yeast surface display and neutralization escape, cell culture inhibition assays were performed with homologous and heterologous strains, and prophylactic and therapeutic activity was evaluated with two mouse models. Protective MAbs localized to epitopes on the lateral ridge of domain I (DI), the dimer interface, lateral ridge, and fusion loop of DII, and the lateral ridge, C-C′ loop, and A strand of DIII. Several MAbs inefficiently inhibited at least one DENV-2 strain of a distinct genotype, suggesting that recognition of neutralizing epitopes varies with strain diversity. Moreover, antibody potency generally correlated with a narrowed genotype and serotype specificity. Five MAbs functioned efficiently as postexposure therapy when administered as a single dose, even 3 days after intracranial infection of BALB/c mice. Overall, these studies define the structural and functional complexity of antibodies against DENV-2 with protective potential.
Mycobacterium tuberculosisPromotes HIVtrans-Infection and Suppresses Major Histocompatibility Complex Class II Antigen Processing by Dendritic Cells
Authors: Reuter Morgan A. , Pecora Nicole D. , Harding Clifford V. , Canaday David H. , McDonald David 
Published: July 2010

ABSTRACTMycobacteriumtuberculosisis a leading killer of HIV-infected individuals worldwide, particularly in sub-Saharan Africa, where it is responsible for up to 50% of HIV-related deaths. Infection by HIV predisposes individuals toM. tuberculosisinfection, and coinfection accelerates the progression of both diseases. In contrast to most other opportunistic infections associated with HIV, an increased risk ofM. tuberculosisinfection occurs during early-stage HIV disease, long before CD4 T cell counts fall below critical levels. We hypothesized thatM. tuberculosisinfection contributes to HIV pathogenesis by interfering with dendritic cell (DC)-mediated immune control. DCs carry pathogens likeM. tuberculosisand HIV from sites of infection into lymphoid tissues, where they process and present antigenic peptides to CD4 T cells. Paradoxically, DCs can also deliver infectious HIV to T cells without first becoming infected, a process known astrans-infection. Lipopolysaccharide (LPS)-activated DCs sequester HIV in pocketlike membrane invaginations that remain open to the cell surface, and individual virions are delivered from the pocket into T cells at the site of contact duringtrans-infection. Here we report thatM. tuberculosisexposure increases HIVtrans-infection and induces viral sequestration within surface-accessible compartments identical to those seen in LPS-stimulated DCs. At the same time,M. tuberculosisdramatically decreases the degradative processing and major histocompatibility complex class II (MHC-II) presentation of HIV antigens to CD4 T cells. Our data suggest thatM. tuberculosisinfection promotes a shift in the dynamic balance between antigen processing and intact virion presentation, favoring DC-mediated amplification of HIV infections.
Population density and mortality among individuals in motor vehicle crashes
Authors: Gedeborg Rolf , Thiblin Ingemar , Byberg Liisa , Melhus Håkan , Lindbäck Johan , Michaelsson Karl 
Published: July 2010

ObjectiveTo assess whether higher mortality rates among individuals in motor vehicle crashes in areas with low population density depend on injury type and severity or are related to the performance of emergency medical services (EMS).MethodsPrehospital and hospital deaths were studied in a population-based cohort of 41 243 motor vehicle crashes that occurred in Sweden between 1998 and 2004. The final multivariable analysis was restricted to 6884 individuals in motor vehicle crashes, to minimise the effects of confounding factors.ResultsCrude mortality rates following motor vehicle crashes were inversely related to regional population density. In regions with low population density, the unadjusted rate ratio for prehospital death was 2.2 (95% CI 1.9 to 2.5) and for hospital death 1.5 (95% CI 1.1 to 1.9), compared with a high-density population. However, after controlling for regional differences in age, gender and the type/severity of injuries among 6884 individuals in motor vehicle crashes, low population density was no longer associated with increased mortality. At 25 years of age, predicted prehospital mortality was 9% lower (95% CI 5% to 12%) in regions with low population density compared with high population density. This difference decreased with increasing age, but was still 3% lower (95% CI 0.5% to 5%) at 65 years of age.ConclusionsThe inverse relationship between population density and mortality among individuals in motor vehicle crashes is related to pre-crash factors that influence the type and severity of injuries and not to differences in EMS.
Evaluation of touch preparation cytology during frozen-section diagnoses of pulmonary lesions
Authors: Rakha E A , Haider A , Patil S , Fourtan H , Chaudry Z , Soomro I N 
Published: July 2010

BackgroundIntraoperative frozen section (FS) examination in thoracic surgery is a reliable method for diagnosis and staging of pulmonary lesions and provides a valuable guide in directing the extent of the ongoing surgical procedure. However, the contribution of touch preparation cytology (TPC) to FS diagnosis remains unclear.AimTo assess the utility of routinely performed TPC during FS diagnoses of pulmonary lesions.MethodsIn this study FS and TPC for all patients who had undergone FS diagnoses of pulmonary lesions in a 6-year period were reviewed by two pathologists.ResultsA total of 155 consecutive patients underwent intraoperative FS procedure, and 110 of those cases had TPC available for review. TPC was diagnostic or contributory to FS diagnosis in 97 (88%) cases, and non-contributory in 13 cases, mainly due to low or inadequate cellularity. TPC provided useful information regarding tumour subtyping, but it was less sensitive in the diagnosis of mucinous neoplasms and was less specific in the assessment of bronchial resection margins. In granulomatous lesions with or without necrosis, TPC was diagnostic in 10 (91%) cases. In five cases (including four cases of tuberculosis), TPC was the only diagnostic tool since FS was not completed. In conclusion, TPC showed high sensitivity and specificity rates and was contributory to FS diagnosis of pulmonary lesions. TPC provides a fast, less-expensive method of diagnosis, utilises a minimal amount of tissue, and can save processing of fresh frozen tissues in certain situations such as tuberculous lesions.
More specific bands in the IgG western blot in sera from Scottish patients with suspected Lyme borreliosis
Authors: Evans Roger , Mavin Sally , McDonagh Susan , Chatterton Jean M W , Milner Rachel , Ho-Yen Darrel O 
Published: July 2010

AimsTo identify further Western blot bands that may be specific in the diagnosis of Lyme borreliosis.MethodsTheBorrelia burgdorferiantibody profiles of 270 western blot positive patients and 241 western blot negative patients from 2008 were examined.Results27 different non-specific bands were detected in both groups. Six of 27 (22%) of the non-specific bands were detected significantly more in the western blot positive patients compared to the western blot negative patients (20 kDa, p<0.0001; 28 kDa, p<0.002; 36 kDa, p<0.002; 37 kDa, p<0.007; 48 kDa, p<0.023; 56 kDa, p<0.028; two-tailed F test).ConclusionResults suggest that the 20, 28 and 48 kDa bands should be regarded as specific.