bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective Survey of (1→3)-β-
d
-Glucan and Its Relationship to Invasive Candidiasis in the Surgical Intensive Care Unit Setting
Authors: Mohr John F. , Sims Charles , Paetznick Victor , Rodriguez Jose , Finkelman Malcolm A. , Rex John H. , Ostrosky-Zeichner Luis 
Published: November 2010

ABSTRACT

Non-culture-based diagnostic strategies are needed for diagnosing invasive candidiasis (IC). We evaluated serial serum (1→3)-β-
d
-glucan (BG) levels in patients in the surgical trauma intensive care unit (SICU) patients with clinical evidence of IC. Serum samples from patients admitted to the SICU for a minimum of 3 days were collected twice weekly and analyzed for BG by using a Fungitell kit with a positive cutoff of ≥80 pg/ml. Diagnosis of IC was done using a set of predefined and validated clinical practice-based criteria. A total of 57 patients consented to participate and were enrolled. The median ICU stay was 16 days (range, 3 to 51). A total of 14 of 57 (25%) false positives were observed in the first sample (ICU day 3) and, overall, 73% of the day 3 samples had higher BG levels than subsequent samples. On the date of clinical diagnosis of IC, the sensitivity of a positive BG for identifying invasive candidiasis was 87%, with a 73% specificity. In patients with evidence of IC, the median BG value was significantly higher than those without evidence of IC (171 versus 48 pg/ml,
P
= 0.02), respectively. In the three patients with proven IC, BG was detected 4 to 8 days prior to diagnosis. BG serum detection may be a useful tool to aid in the early diagnosis of IC in SICU patients, particularly after day 3 and in patients with at least two positive samples drawn several days apart. Elevated BG levels within the first 3 days need to be further characterized.
Inverse Association between Lancefield Group G
Streptococcus
Colonization and Sore Throat in Slum and Nonslum Settings in Brazil
Authors: Tartof Sara Yee , Farrimond Frances , de Matos Juliana Arruda , Reis Joice Neves , Ramos Regina Terse Trindade , Andrade Aurelio Nei , dos Reis Mitermayer Galvão , Riley Lee Woodland 
Published: November 2010

ABSTRACT

Group G
Streptococcus
has been implicated as a causative agent of pharyngitis in outbreak situations, but its role in endemic disease remains elusive. We found an unexpected inverse association of
Streptococcus dysgalactiae
subsp.
equisimilis
colonization and sore throat in a study of 2,194 children of 3 to 15 years of age in Salvador, Brazil.
Modification of Nonstructural Protein 1 of Influenza A Virus by SUMO1
Authors: Xu Ke , Klenk Christoph , Liu Bin , Keiner Bjoern , Cheng Jinke , Zheng Bo-Jian , Li Li , Han Qinglin , Wang Chen , Li Tianxian , Chen Ze , Shu Yuelong , Liu Jinhua , Klenk Hans-Dieter , Sun Bing 
Published: November 2010

ABSTRACT
Nonstructural protein 1 (NS1) is one of the major factors resulting in the efficient infection rate and high level of virulence of influenza A virus. Although consisting of only approximately 230 amino acids, NS1 has the ability to interfere with several systems of the host viral defense. In the present study, we demonstrate that NS1 of the highly pathogenic avian influenza A/Duck/Hubei/L-1/2004 (H5N1) virus interacts with human Ubc9, which is the E2 conjugating enzyme for sumoylation, and we show that SUMO1 is conjugated to H5N1 NS1 in both transfected and infected cells. Furthermore, two lysine residues in the C terminus of NS1 were identified as SUMO1 acceptor sites. When the SUMO1 acceptor sites were removed by mutation, NS1 underwent rapid degradation. Studies of different influenza A virus strains of human and avian origin showed that the majority of viruses possess an NS1 protein that is modified by SUMO1, except for the recently emerged swine-origin influenza A virus (S-OIV) (H1N1). Interestingly, growth of a sumoylation-deficient WSN virus mutant was retarded compared to that of wild-type virus. Together, these results indicate that sumoylation enhances NS1 stability and thus promotes rapid growth of influenza A virus.
Comprehensive Analysis of Frequency and Phenotype of T Regulatory Cells in HIV Infection: CD39 Expression of FoxP3+T Regulatory Cells Correlates with Progressive Disease
Authors: Schulze zur Wiesch Julian , Thomssen Adriana , Hartjen Philip , Tóth Ilona , Lehmann Clara , Meyer-Olson Dirk , Colberg Kristina , Frerk Sebastian , Babikir Dalia , Schmiedel Stefan , Degen Olaf , Mauss Stefan , Rockstroh Jürgen , Staszewski Schlomo , Khaykin Pavel , Strasak Alexander , Lohse Ansgar W. , Fätkenheuer Gerd , Hauber Joachim , van Lunzen Jan 
Published: November 2010

ABSTRACTThere are conflicting data about the frequency and role of regulatory T cells (Tregs) during the course of HIV infection. Peripheral blood of a large cohort of HIV-infected patients (n= 131) at different stages of disease, including 15 long-term nonprogressors and 21 elite controllers, was analyzed to determine the frequency and phenotype of Tregs, defined as CD4+, CD25high, CD127low, FoxP3highcells. A significantly increased relative frequency of Tregs within the CD4+compartment of HIV+patients compared to that of healthy controls (P< 0.0001) was observed. Additionally, the relative frequency of Tregs directly correlated with HIV viral load and inversely with CD4+counts. However, the absolute Treg number was reduced in HIV-infected patients versus healthy controls (P< 0.0001), with the exception of elite controllers (P> 0.05). The loss of absolute Treg numbers coincided with rising markers of immune activation (P< 0.0006). The initiation of antiviral therapy significantly increased absolute Treg numbers (P< 0.0031). We find that the expression of CD39, a newly defined ectonucleotidase with immunomodulatory functions on Tregs, correlated with progressive HIV disease, HIV viral load, and immune activation. Of note, when tested in peripheral blood mononuclear cells of healthy volunteers, thein vitrocapacity to suppress T-cell proliferation was limited to CD4+, CD25high, CD39+T cells. Interestingly, Tregs of elite controllers exhibited not only the highest expression of CCR5, CTLA-4, and ICOS but also the lowest level of CD39. The data presented here reconcile the seemingly contradictory results of previous studies looking at Tregs in HIV and highlight the complexity of Treg-mediated immunoregulation during human viral infections.
Alphacoronavirus Transmissible Gastroenteritis Virus nsp1 Protein Suppresses Protein Translation in Mammalian Cells and in Cell-Free HeLa Cell Extracts but Not in Rabbit Reticulocyte Lysate
Authors: Huang Cheng , Lokugamage Kumari G. , Rozovics Janet M. , Narayanan Krishna , Semler Bert L. , Makino Shinji 
Published: November 2010

ABSTRACT
The nsp1 protein of transmissible gastroenteritis virus (TGEV), an alphacoronavirus, efficiently suppressed protein synthesis in mammalian cells. Unlike the nsp1 protein of severe acute respiratory syndrome coronavirus, a betacoronavirus, the TGEV nsp1 protein was unable to bind 40S ribosomal subunits or promote host mRNA degradation. TGEV nsp1 also suppressed protein translation in cell-free HeLa cell extract; however, it did not affect translation in rabbit reticulocyte lysate (RRL). Our data suggested that HeLa cell extracts and cultured host cells, but not RRL, contain a host factor(s) that is essential for TGEV nsp1-induced translational suppression.
Human Cytomegalovirus UL47 Tegument Protein Functions after Entry and before Immediate-Early Gene Expression
Authors: Bechtel Jill T. , Shenk Thomas 
Published: October 2010

ABSTRACT

The human cytomegalovirus UL47 open reading frame encodes a 110-kDa protein that is a component of the virion tegument. We have constructed a cytomegalovirus mutant, AD
sub
UL47, in which the central portion of the UL47 open reading frame has been replaced by two marker genes. The mutant replicated to titers 100-fold lower than those for wild-type virus after infection at either a high or a low input multiplicity in primary human fibroblasts but was substantially complemented on cells expressing UL47 protein. A revertant virus in which the mutation was repaired, AD
rev
UL47, replicated with wild-type kinetics. Mutant virions lacked UL47 protein and contained reduced amounts of UL48 protein. The mutant was found to be less infectious than wild-type virus, and a defect very early in the replication cycle was observed. Transcription of the viral immediate-early 1 gene was delayed by 8 to 10 h. However, this delay was not the result of a defect in virus entry or of the inability of virion proteins to transactivate the major immediate-early promoter. We also show that the UL47 protein coprecipitated with the UL48 and UL69 tegument proteins and the UL86-encoded major capsid protein. We propose that a UL47-containing complex is involved in the release of viral DNA from the disassembling virus particle and that the loss of UL47 protein causes this process to be delayed.
Protective Effect of Avian Myelomonocytic Growth Factor in Infection with Marek’s Disease Virus
Authors: Djeraba Aouatef , Musset Eugène , Lowenthal John W. , Boyle David B. , Chaussé Anne-Marie , Péloille Michele , Quéré Pascale 
Published: October 2010

ABSTRACTMarek’s disease virus (MDV) is a herpesvirus that induces T lymphomas in chickens. The aim of this study was to assess the role of the macrophage activator chicken myelomonocytic growth factor (cMGF) in controlling MDV infection. B13/B13 chickens, which are highly susceptible to MD, were either treated with cMGF delivered via a live fowlpox virus (fp/cMGF) or treated with the parent vector (fp/M3) or were left as untreated controls. Seven days later, when challenged with the very virulent RB-1B strain of MDV, the spleens of chickens treated with fp/cMGF showed increased expression of the inducible nitric oxide synthase (iNOS) gene compared to those of control chickens and fp/M3-treated chickens. Increased iNOS gene expression was also accompanied by greater induction of gamma interferon and macrophage inflammatory protein (K203) gene expression, both possible activators of iNOS. fp/cMGF treatment also increased the number of monocytes and systemic NO production in contrast to fp/M3 treatment. Even though cMGF treatment was unable to prevent death for the chickens, it did prolong their survival time, and viremia and tumor incidence were greatly reduced. In addition, cMGF treatment improved the partial protection induced by vaccination with HVT (herpesvirus isolated from turkeys) against RB-1B, preventing 100% mortality (versus 66% with vaccination alone) and greatly reducing tumor development. Treatment with fp/M3 did not have such effects. These results suggest that cMGF may play multiple roles in protection against MD. First, it may enhance the innate immune response by increasing the number and activity of monocytes and macrophages, resulting in increased NO production. Second, it may enhance the acquired immune response, indicated by its ability to enhance vaccine efficacy.
Inhibition of Interferons by Ectromelia Virus
Authors: Smith Vincent P. , Alcami Antonio 
Published: October 2010

ABSTRACTEctromelia virus (EV) is an orthopoxvirus (OPV) that causes mousepox, a severe disease of laboratory mice. Mousepox is a useful model of OPV infection because EV is likely to be a natural mouse pathogen, unlike its close relatives vaccinia virus (VV) and variola virus. Several studies have highlighted the importance of mouse interferons (IFNs) in resistance to and recovery from EV infection, but little is known of the anti-IFN strategies encoded by the virus itself. We have determined that 12 distinct strains and isolates of EV encode soluble, secreted receptors for IFN-γ (vIFN-γR) and IFN-α/β (vIFN-α/βR) that are homologous to those identified in other OPVs. We demonstrate for the first time that the EV vIFN-γR has the unique ability to inhibit the biological activity of mouse IFN-γ. The EV vIFN-α/βR was a potent inhibitor of human and mouse IFN-α and human IFN-β but, surprisingly, was unable to inhibit mouse IFN-β. The replication of all of the EVs included in our study and of cowpox virus was more resistant than VV to the antiviral effects induced in mouse L-929 cells by IFN-α/β and IFN-γ. Sequencing studies showed that this EV resistance is likely to be partly mediated by the double-stranded-RNA-binding protein encoded by an intact EV homolog of the VV E3L gene. The absence of a functional K3L gene, which encodes a viral eIF-2α homolog, in EV suggests that the virus encodes a novel mechanism to counteract the IFN response. These findings will facilitate future studies of the role of viral anti-IFN strategies in mousepox pathogenesis. Their significance in the light of earlier data on the role of IFNs in mousepox is discussed.
A Six-Nucleotide Segment within the 3′ Untranslated Region of Hibiscus Chlorotic Ringspot Virus Plays an Essential Role in Translational Enhancement
Authors: Koh Dora Chin-Yen , Liu D. X. , Wong Sek-Man 
Published: October 2010

ABSTRACT

RNA plant viruses use various translational regulatory mechanisms to control their gene expression. Translational enhancement of viral mRNAs that leads to higher levels of protein synthesis from specific genes may be essential for the virus to successfully compete for cellular translational machinery. The control elements have yet to be analyzed for members of the genus
Carmovirus
, a small group of plant viruses with positive-sense RNA genomes. In this study, we examined the 3′ untranslated region (UTR) of hibiscus chlorotic ringspot virus (HCRSV) genomic RNA (gRNA) and subgenomic RNA (sgRNA) for its role in the translational regulation of viral gene expression. The results showed that the 3′ UTR of HCRSV significantly enhanced the translation of several open reading frames on gRNA and sgRNA and a viral gene in a bicistronic construct with an inserted internal ribosome entry site. Through deletion and mutagenesis studies of both the bicistronic construct and full-length gRNA, we demonstrated that a six-nucleotide sequence, GGGCAG, that is complementary to the 3′ region of the 18S rRNA and a minimal length of 180 nucleotides are required for the enhancement of translation induced by the 3′ UTR.
Effects of Influenza A Virus NS1 Protein on Protein Expression: the NS1 Protein Enhances Translation and Is Not Required for Shutoff of Host Protein Synthesis
Authors: Salvatore Mirella , Basler Christopher F. , Parisien Jean-Patrick , Horvath Curt M. , Bourmakina Svetlana , Zheng Hongyong , Muster Thomas , Palese Peter , García-Sastre Adolfo 
Published: October 2010

ABSTRACT
The influenza A virus NS1 protein, a virus-encoded alpha/beta interferon (IFN-α/β) antagonist, appears to be a key regulator of protein expression in infected cells. We now show that NS1 protein expression results in enhancement of reporter gene activity from transfected plasmids. This effect appears to be mediated at the translational level, and it is reminiscent of the activity of the adenoviral virus-associated I (VAI) RNA, a known inhibitor of the antiviral, IFN-induced, PKR protein. To study the effects of the NS1 protein on viral and cellular protein synthesis during influenza A virus infection, we used recombinant influenza viruses lacking the NS1 gene (delNS1) or expressing truncated NS1 proteins. Our results demonstrate that the NS1 protein is required for efficient viral protein synthesis in COS-7 cells. This activity maps to the amino-terminal domain of the NS1 protein, since cells infected with wild-type virus or with a mutant virus expressing a truncated NS1 protein—lacking approximately half of its carboxy-terminal end—showed similar kinetics of viral and cellular protein expression. Interestingly, no major differences in host cell protein synthesis shutoff or in viral protein expression were found among NS1 mutant viruses in Vero cells. Thus, another viral component(s) different from the NS1 protein is responsible for the inhibition of host protein synthesis during viral infection. In contrast to the earlier proposal suggesting that the NS1 protein regulates the levels of spliced M2 mRNA, no effects on M2 protein accumulation were seen in Vero cells infected with delNS1 virus.
Mutations of the Woodchuck Hepatitis Virus Polymerase Gene That Confer Resistance to Lamivudine and 2′-Fluoro-5-Methyl-β-
l
-Arabinofuranosyluracil
Authors: Yamamoto Toshiki , Litwin Samuel , Zhou Tianlun , Zhu Yuao , Condreay Lynn , Furman Phillip , Mason William S. 
Published: October 2010

ABSTRACT

Administration of either lamivudine (2′-deoxy-3′-thiacytidine) or
l
-FMAU (2′-fluoro-5-methyl-β-
l
-arabinofuranosyluracil) to woodchucks chronically infected with woodchuck hepatitis virus (WHV) induces a transient decline in virus titers. However, within 6 to 12 months, virus titers begin to increase towards pretreatment levels. This is associated with the emergence of virus strains with mutations of the B and C regions of the viral DNA polymerase (T. Zhou et al., Antimicrob. Agents Chemother. 43:1947–1954, 1999; Y. Zhu et al., J. Virol. 75:311–322, 2001). The present study was carried out to determine which of the mutants that we have identified conferred resistance to lamivudine and/or to
l
-FMAU. When inserted into a laboratory strain of WHV, each of the mutations, or combinations of mutations, of regions B and C produced a DNA replication-competent virus and typically conferred resistance to both nucleoside analogs in cell culture. Sequencing of the polymerase active site also occasionally revealed other mutations, but these did not appear to contribute to drug resistance. Moreover, in transfected cells, most of the mutants synthesized viral DNA nearly as efficiently as wild-type WHV. Computational models suggested that persistence of several of the WHV mutants as prevalent species in the serum and, by inference, liver for up to 6 months following drug withdrawal required a replication efficiency of at least 10 to 30% of that of the wild type. However, their delayed emergence during therapy suggested replication efficiency in the presence of the drug that was still well below that of wild-type WHV in the absence of the drug.
Proteolytic Processing of Human Cytomegalovirus Glycoprotein B Is Dispensable for Viral Growth in Culture
Authors: Strive Tanja , Borst Eva , Messerle Martin , Radsak Klaus 
Published: October 2010

ABSTRACT
Glycoprotein B (gB) of human cytomegalovirus (HCMV), which is considered essential for the viral life cycle, is proteolytically processed during maturation. Since gB homologues of several other herpesviruses remain uncleaved, the relevance of this property of HCMV gB for viral infectivity is unclear. Here we report on the construction of a viral mutant in which the recognition site of gB for the cellular endoprotease furin was destroyed. Because mutagenesis of essential proteins may result in a lethal phenotype, a replication-deficient HCMV gB-null genome encoding enhanced green fluorescent protein was constructed, and complementation by mutant gBs was initially evaluated in transient-cotransfection assays. Cotransfection of plasmids expressing authentic gB or gB with a mutated cleavage site (gB-ΔFur) led to the formation of green fluorescent miniplaques which were considered to result from one cycle of phenotypic complementation of the gB-null genome. To verify these results, two recombinant HCMV genomes were constructed: HCMV-BAC-ΔMhdI, with a deletion of hydrophobic domain 1 of gB that appeared to be essential for viral growth in the cotransfection experiments, and HCMV-BACΔFur, in which the gB cleavage site was mutated by amino acid substitution. Consistent with the results of the cotransfection assays, only the ΔFur mutant replicated in human fibroblasts, showing growth kinetics comparable to that of wild-type virus. gB in mutant-infected cells was uncleaved, whereas glycosylation and transport to the cell surface were not impaired. Extracellular mutant virus contained exclusively uncleaved gB, indicating that proteolytic processing of gB is dispensable for viral replication in cell culture.
Detection of a Novel Unglycosylated Form of Hepatitis C Virus E2 Envelope Protein That Is Located in the Cytosol and Interacts with PKR
Authors: Pavio Nicole , Taylor Deborah R. , Lai Michael M. C. 
Published: October 2010

ABSTRACT
The hepatitis C virus (HCV) envelope protein E2 has been shown to accumulate in the lumen of the endoplasmic reticulum (ER) as a properly folded glycoprotein as well as large aggregates of misfolded proteins. In the present study, we have identified an additional unglycosylated species, with an apparent molecular mass of 38 kDa (E2-p38). In contrast to the glycosylated E2, E2-p38 is significantly less stable and is degraded through the proteasome pathway. Correspondingly, E2-p38 is found to be ubiquitinated. E2-p38 is localized mostly in the cytosol, in contrast to the glycosylated form, which is exclusively membrane associated. Alpha interferon (IFN-α) treatment or overexpression of the double-stranded RNA-activated protein kinase (PKR) significantly increased the stability of E2-p38, consistent with a previous report (D. R. Taylor, S. T. Shi, P. R. Romano, G. N. Barber, and M. M. Lai, Science 285:107–110, 1999) that E2 interacts with PKR and inhibits its kinase activity. Direct interaction between PKR and E2-p38, but not the glycosylated form of E2, was also observed. These results show that E2-p38 is the form of E2 that interacts with PKR in the cytosol and may contribute to the resistance of HCV to IFN-α. Thus, an ER protein can exist in the cytosol as an unglycosylated species and impair cellular functions.
Complement Component C1q Enhances the Biological Activity of Influenza Virus Hemagglutinin-Specific Antibodies Depending on Their Fine Antigen Specificity and Heavy-Chain Isotype
Authors: Feng Jing Qi , Mozdzanowska Krystyna , Gerhard Walter 
Published: October 2010

ABSTRACTWe have previously observed that selected influenza virus hemagglutinin (HA)-specific monoclonal antibodies (MAbs) with poor virus-neutralizing (VN) activity in vitro exhibited greatly enhanced VN activity in vivo after administration to SCID mice. The same Abs displayed improved VN activity also when tested in vitro in the presence of noninactivated serum from SCID mice. To identify Ab-dependent properties and serum components that contributed to enhancement of Ab activity, we screened a large panel of HA-specific MAbs for hemagglutination inhibition (HI) in the presence of noninactivated serum from naive mice (NMS). We found that HI activity was enhanced by NMS depending on the Ab’s fine specificity (antigenic region Cb/E > Ca/A,D > Sa,Sb/B), its heavy-chain isotype (immunoglobulin G2 [IgG2] > IgG3; IgG1 and IgM negative), and to some extent also on its derivation (primary response > memory response). On average, the HI activity of Cb/E-specific MAbs of the IgG2 isotype isolated from the primary response was enhanced by 20-fold. VN activity was enhanced significantly but less strongly than HI activity. Enhancement (i) was destroyed by heat inactivation (30 min, 56°C); (ii) did not require C3, the central complement component; (iii) was abolished by treatment of serum with anti-C1q; and (iv) could be reproduced with purified C1q, the binding moiety of C1, the first complement component. We believe that this is the first description of a direct C1q-mediated enhancement of antiviral Ab activities.