bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors Characterizing
Staphylococcus epidermidis
Invasiveness Determined by Comparative Genomics
Authors: Yao Yufeng , Sturdevant Daniel E. , Villaruz Amer , Xu Lin , Gao Qian , Otto Michael 
Published: February 2005

ABSTRACT

Virulence mechanisms of the leading nosocomial pathogen
Staphylococcus epidermidis
are poorly understood. We used microarray-based genome-wide comparison of clinical and commensal
S. epidermidis
strains to identify putative virulence determinants. Our study revealed high genetic variability of the
S. epidermidis
genome, new markers for invasiveness of
S. epidermidis
, and potential targets for drug development against
S. epidermidis
infections.
Sublethal Infection of C57BL/6 Mice with
Salmonella enterica
Serovar Typhimurium Leads to an Increase in Levels of Toll-Like Receptor 1 (TLR1), TLR2, and TLR9 mRNA as Well as a Decrease in Levels of TLR6 mRNA in Infected Organs
Authors: Tötemeyer Sabine , Kaiser Pete , Maskell Duncan J. , Bryant Clare E. 
Published: February 2005

ABSTRACT

Sublethal infection of C57BL/6 mice with
Salmonella enterica
serovar Typhimurium M525P initiates a strong inflammatory response. We measured organ expression of mRNA for Toll-like receptors and their associated signaling molecules during
S. enterica
serovar Typhimurium infection. During infection, the Toll-lie receptor 1 (TLR1), TLR2, and TLR9 mRNA levels increased, while TLR6 mRNA expression decreased.
GeneChip Analyses of Global Transcriptional Responses of Murine Macrophages to the Lethal Toxin ofBacillus anthracis
Authors: Comer Jason E. , Galindo Cristi L. , Chopra Ashok K. , Peterson Johnny W. 
Published: February 2005

ABSTRACTWe performed GeneChip analyses on RNA fromBacillus anthracislethal toxin (LeTx)-treated RAW 264.7 murine macrophages to investigate global effects of anthrax toxin on host cell gene expression. Stringent analysis of data revealed that the expression of several mitogen-activated protein kinase kinase-regulatory genes was affected within 1.5 h post-exposure to LeTx. By 3.0 h, the expression of 103 genes was altered, including those involved in intracellular signaling, energy production, and protein metabolism.
Mycobacterium tuberculosis
with Disruption in Genes Encoding the Phosphate Binding Proteins PstS1 and PstS2 Is Deficient in Phosphate Uptake and Demonstrates Reduced In Vivo Virulence
Authors: Peirs Priska , Lefèvre Philippe , Boarbi Samira , Wang Xiao-Ming , Denis Olivier , Braibant Martine , Pethe Kevin , Locht Camille , Huygen Kris , Content Jean 
Published: February 2005

ABSTRACT

By measuring phosphate uptake by
Mycobacterium tuberculosis
strains with the
pstS1
and
pstS2
genes genetically inactivated, we showed that these
pstS
genes encode high-affinity phosphate binding proteins. In a mouse infection model, both mutants were attenuated in virulence, suggesting that
M. tuberculosis
encounters limiting phosphate concentrations during its intracellular life span.
Mice Fed Lipid-Encapsulated
Mycobacterium bovis
BCG Are Protected against Aerosol Challenge with
Mycobacterium tuberculosis
Authors: Aldwell Frank E. , Brandt Lise , Fitzpatrick Clare , Orme Ian M. 
Published: February 2005

ABSTRACT

Mice that consumed a single dose of 10
7
lipid-encapsulated
Mycobacterium bovis
BCG bacilli showed significant pulmonary and systemic protection against aerosol challenge with
M. tuberculosis
H37Rv. As an extension of previous challenge studies with virulent strains of
M. bovis
, this report describes a reduction in
M. tuberculosis
infection in mice vaccinated orally with lipid-encapculated BCG comparable to that observed in mice vaccinated subcutaneously with BCG. These results are consistent with the induction of tuberculin-specific cell-mediated immune responses.
Dual Mechanisms of Pestiviral Superinfection Exclusion at Entry and RNA Replication
Authors: Lee Young-Min , Tscherne Donna M. , Yun Sang-Im , Frolov Ilya , Rice Charles M. 
Published: February 2005

ABSTRACTFor many viruses, primary infection has been shown to prevent superinfection by a homologous second virus. In this study, we investigated superinfection exclusion of bovine viral diarrhea virus (BVDV), a positive-sense RNA pestivirus. Cells acutely infected with BVDV were protected from superinfection by homologous BVDV but not with heterologous vesicular stomatitis virus. Superinfection exclusion was established within 30 to 60 min but was lost upon passaging of persistently infected cells. Superinfecting BVDV failed to deliver a translatable genome into acutely infected cells, indicating a block in viral entry. Deletion of structural protein E2 from primary infecting BVDV abolished this exclusion. Bypassing the entry block by RNA transfection revealed a second block at the level of replication but not translation. This exclusion did not require structural protein expression and was inversely correlated with the level of primary BVDV RNA replication. These findings suggest dual mechanisms of pestivirus superinfection exclusion, one at the level of viral entry that requires viral glycoprotein E2 and a second at the level of viral RNA replication.
E1A-CR3 Interaction-Dependent and -Independent Functions of mSur2 in Viral Replication of Early Region 1A Mutants of Mouse Adenovirus Type 1
Authors: Fang Lei , Spindler Katherine R. 
Published: February 2005

ABSTRACTmSur2, a subunit of the Mediator complex, is required for efficient mouse adenovirus type 1 (MAV-1) replication (L. Fang, J. L. Stevens, A. J. Berk, and K. R. Spindler, J. Virol.78:12888-12900, 2004). We examined the contributions of early-region 1A (E1A) to mSur2 function in MAV-1 replication with E1A mutant viruses. At a multiplicity of infection (MOI) of 1, viruses containing CR3 replicated better in Sur2+/+mouse embryonic fibroblasts (MEFs) than in Sur2−/−MEFs. In contrast, viruses lacking CR3 replicated no better in Sur2+/+than in Sur2−/−MEFs. This result supports the hypothesis that the E1A CR3-mSur2 interaction is important for MAV-1 replication. However, at an MOI of 0.05, viruses lacking CR3 showed replication defects in Sur2−/−MEFs compared to Sur2+/+MEFs, suggesting an E1A CR3 interaction-independent function of mSur2 in MAV-1 replication in cell culture. Paradoxically, CR1Δ, CR2Δ, and CR3Δ mutant viruses replicated slightly more efficiently than wild-type (wt) MAV-1 and E1A null mutant viruses in Sur2−/−MEFs at an MOI of 0.05. Coinfection of Sur2−/−MEFs with wt MAV-1 and CR1Δ, CR2Δ, or CR3Δ mutant viruses rescued the defects of wt MAV-1 replication. This result suggests that an inhibiting effect on wt E1A protein expression and/or E1A function might account for the severe viral replication defect of MAV-1 in Sur2−/−MEFs at an MOI of 0.05. Moreover, titrations of virus yields from infected brains of inbred strains of mice showed that E1A null and CR3Δ mutant viruses had a significant defect in virus replication compared to wt MAV-1. This result supports the hypothesis that the MAV-1 E1A-mSur2 interaction is important in MAV-1 replication in mice.
Recombinant Herpes Simplex Virus Type 1 (HSV-1) Codelivering Interleukin-12p35 as a Molecular Adjuvant Enhances the Protective Immune Response against Ocular HSV-1 Challenge
Authors: Osorio Yanira , Ghiasi Homayon 
Published: February 2005

ABSTRACTAn important aspect of ocular herpes simplex virus type 1 (HSV-1) vaccine development is identification of an appropriate adjuvant capable of significantly reducing both virus replication in the eye and explant reactivation in trigeminal ganglia. We showed recently that a recombinant HSV-1 vaccine expressing interleukin-4 (IL-4) is more efficacious against ocular HSV-1 challenge than recombinant viruses expressing IL-2 or gamma interferon (IFN-γ) (Y. Osorio and H. Ghiasi, J. Virol. 77:5774-5783, 2003). We have now constructed and compared recombinant HSV-1 viruses expressing IL-12p35 or IL-12p40 molecule with IL-4-expressing HSV-1 recombinant virus. BALB/c mice were immunized intraperitoneally with IL-12p35-, IL-12p40-, IL-12p35+IL-12p40-, or IL-4-expressing recombinant HSV-1 viruses. Controls included mice immunized with parental virus and mice immunized with the avirulent strain KOS. The efficacy of each vaccine in protecting against ocular challenge with HSV-1 was assessed in terms of survival, eye disease, virus replication in the eye, and explant reactivation. Neutralizing antibody titers, T-cell responses, and expression of 32 cytokines and chemokines were also evaluated. Mice immunized with recombinant HSV-1 expressing IL-12p35 exhibited the lowest virus replication in the eye, the most rapid virus clearance, and the lowest level of explant reactivation. The higher efficacy against ocular virus replication and explant reactivation correlated with higher neutralizing antibody titers, cytotoxic-T-lymphocyte activities, and IFN-γ expression in recombinant HSV-1 expressing IL-12p35 compared to other vaccines. Mice immunized with both IL-12p35 and IL-12p40 had lower neutralizing antibody responses than mice immunized with IL-12p35 alone. Our results confirm that recombinant virus vaccines expressing cytokine genes can enhance the overall protection against infection, with the IL-12p35 vaccine being the most efficacious of those tested. Collectively, the results support the potential use of IL-12p35 as a vaccine adjuvant, without the toxicity-associated concerns of IL-12.
Modulation of the CD8+-T-Cell Response by CD4+CD25+Regulatory T Cells in Patients with Hepatitis B Virus Infection
Authors: Franzese Ornella , Kennedy Patrick T. F. , Gehring Adam J. , Gotto Jim , Williams Roger , Maini Mala K. , Bertoletti Antonio 
Published: February 2005

ABSTRACTCD4+CD25+regulatory T cells have been shown to maintain peripheral tolerance against self and foreign antigens. In this study we analyzed the effect of circulating CD4+CD25+T cells on CD8+-T-cell responses of patients with chronic and resolved hepatitis B virus (HBV) infection. We demonstrated that circulating CD4+CD25+T cells modulate the function and expansion of HBV-specific CD8+cells ex vivo in all patients, regardless of whether they have chronic or resolved HBV infection. The possible role of CD4+CD25+T cells in the pathogenesis of chronic HBV infection is not supported by these data. However, these results might have implications for optimizing future immunotherapeutic approaches to HBV treatment.
Altered Function in CD8+T Cells following Paramyxovirus Infection of the Respiratory Tract
Authors: Gray Peter M. , Arimilli Subhashini , Palmer Ellen M. , Parks Griffith D. , Alexander-Miller Martha A. 
Published: February 2005

ABSTRACTFor many respiratory pathogens, CD8+T cells have been shown to play a critical role in clearance. However, there are still many unanswered questions with regard to the factors that promote the most efficacious immune response and the potential for immunoregulation of effector cells at the local site of infection. We have used infection of the respiratory tract with the model paramyxovirus simian virus 5 (SV5) to study CD8+T-cell responses in the lung. For the present study, we report that over time a population of nonresponsive, virus-specific CD8+T cells emerged in the lung, culminating in a lack of function in ∼85% of cells specific for the immunodominant epitope from the viral matrix (M) protein by day 40 postinfection. Concurrent with the induction of nonresponsiveness, virus-specific cells that retained function at later times postinfection exhibited an increased requirement for CD8 engagement. This change was coupled with a nearly complete loss of functional phosphoprotein-specific cells, a response previously shown to be almost exclusively CD8 independent. These studies add to the growing evidence for immune dysregulation following viral infection of the respiratory tract.
Differential Role for TLR3 in Respiratory Syncytial Virus-Induced Chemokine Expression
Authors: Rudd Brian D. , Burstein Ezra , Duckett Colin S. , Li Xiaoxia , Lukacs Nicholas W. 
Published: February 2005

ABSTRACTRespiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in young infants worldwide. Previous studies have reported that the induction of interleukin-8/CXCL8 and RANTES/CCL5 correlates with disease severity in humans. The production of these chemokines is elicited by viral replication and is NF-κB dependent. RSV, a negative-sense single-stranded RNA virus, requires full-length positive-sense RNA for synthesis of new viral RNA. The aim of our studies was to investigate whether active viral replication by RSV could evoke chemokine production through TLR3-mediated signaling pathways. In TLR3-transfected HEK 293 cells, live RSV preferentially activated chemokines in both a time- and dose-dependent manner compared to vector controls. RSV was also shown to upregulate TLR3 in human lung fibroblasts and epithelial cells (MRC-5 and A549). Targeting the expression of TLR3 with small interfering RNA decreased synthesis of IP-10/CXCL10 and CCL5 but did not significantly reduce levels of CXCL8. Blocking the expression of the adapter protein MyD88 established a role for MyD88 in CXCL8 production, whereas CCL5 synthesis was found to be MyD88 independent. Production of CCL5 by RSV was induced directly through TLR3 signaling pathways and did not require interferon (IFN) signaling through the IFN-α/β receptor. TLR3 did not affect viral replication, since equivalent viral loads were recovered from RSV-infected cells despite altered TLR3 expression. Taken together, our studies indicate that TLR3 mediates inflammatory cytokine and chemokine production in RSV-infected epithelial cells.
B-Cell Responses in Patients Who Have Recovered from Severe Acute Respiratory Syndrome Target a Dominant Site in the S2 Domain of the Surface Spike Glycoprotein
Authors: Zhong Xiaofen , Yang Huanghao , Guo Zu-Feng , Sin Wan-Yee Fion , Chen Wei , Xu Junjie , Fu Ling , Wu Jie , Mak Chun-Kit Gannon , Cheng Chak-Sum Samuel , Yang Yanzhen , Cao Shuyong , Wong Tin-Yau , Lai Sik-To , Xie Yong , Guo Zhihong 
Published: February 2005

ABSTRACT
Severe acute respiratory syndrome (SARS) is a recently emerged infectious disease caused by a novel strain of coronavirus. Examination of the immune responses of patients who have recovered from SARS should provide important information for design of a safe and effective vaccine. We determined the continuous viral epitopes targeted by antibodies in plasma samples from convalescent SARS patients through biopanning with a vast M13 phage display dodecapeptide library. These epitopes converged to very short peptide fragments, one on each of the structural proteins spike and nucleocapsid and the nonstructural proteins 3a, 9b, and nsp 3. Immunoassays found that most of the patients who had recovered from SARS developed complementary antibodies to the epitope-rich region on the spike S2 protein, indicating that this is an immunodominant site on the viral envelope comprising the spike, matrix, and small envelope glycoproteins. These S2-targeting antibodies were shown to effectively neutralize the coronavirus, indicating that they provided protective immunity to help the patients recover from the viral infection. These results suggest that the SARS coronavirus might have an antigenic profile distinct from those of other human or animal coronaviruses. Due to the tested safety and protective effects of the convalescent-phase serological antibodies, identification of their complementary antigens may enable the design of an epitope-based vaccine to prevent potential antibody-mediated immunuopathology.
Characterization of an In Vitro Model of Alphavirus Infection of Immature and Mature Neurons
Authors: Vernon Patty S. , Griffin Diane E. 
Published: February 2005

ABSTRACT
Terminally differentiated, mature neurons are essential cells that are not easily regenerated. Neurotropic viruses, such as Sindbis virus (SV), cause encephalomyelitis through their ability to replicate in neurons. SV causes the death of immature neurons, while mature neurons can often survive infection. The lack of a reproducible and convenient neuronal cell culture system has hindered a detailed study of the differences in levels of virus replication between immature and mature neurons and the molecular events involved in virus clearance from mature neurons. We have characterized SV replication in immortalized CSM14.1 rat neuronal cells that can be differentiated into neurons. During differentiation, CSM14.1 cells ceased dividing, developed neuronal morphology, and expressed neuron-specific cell markers. SV infection of undifferentiated CSM14.1 cells was efficient and resulted in high levels of virus replication and cell death. SV infection of differentiated CSM14.1 cells was less efficient and resulted in the production of 10- to 100-fold less virus and cell survival. In undifferentiated cells, SV induced a rapid shutdown of cellular protein synthesis and pE2 was efficiently processed to E2 (ratio of E2 to pE2, 2.14). In differentiated cells, the SV-induced shutdown of cellular protein synthesis was transient and pE2 was the primary form of E2 in cells (ratio of E2 to pE2, 0.0426). We conclude that age-dependent restriction of virus replication is an intrinsic property of maturing neurons and that the CSM14.1 cell line is a convenient model system for investigating the interactions of alphaviruses with neurons at various stages of differentiation.
Kaposi's Sarcoma-Associated Herpesvirus Reactivation Is Regulated by Interaction of Latency-Associated Nuclear Antigen with Recombination Signal Sequence-Binding Protein Jκ, the Major Downstream Effector of the Notch Signaling Pathway
Authors: Lan Ke , Kuppers Daniel A. , Robertson Erle S. 
Published: February 2005

ABSTRACT
Kaposi's sarcoma-associated herpesvirus (KSHV) is the major biological cofactor contributing to development of Kaposi's sarcoma. KSHV establishes a latent infection in human B cells expressing the latency-associated nuclear antigen (LANA), a critical factor in the regulation of viral latency. LANA controls KSHV latent infection through repression of RTA, an activator of many lytic promoters. RTA activates the expression of several lytic viral genes by interacting with recombination signal sequence-binding protein Jκ (RBP-Jκ), a transcriptional repressor and the target of the Notch signaling pathway. The recognition that a number of KSHV lytic gene promoters, including RTA, contain RBP-Jκ binding sites raised the possibility that RBP-Jκ-mediated repression may be central to the establishment of latency. Here, we tested this hypothesis by examining the regulation of RTA by LANA through binding to RBP-Jκ. This study demonstrates that LANA physically associates with RBP-Jκ in vitro and in KSHV-infected cells, with the complex formed capable of binding to RBP-Jκ cognate sequences. RBP-Jκ binding sites within the RTA promoter have been found to be critical for LANA-mediated repression. Our study describes a novel mechanism through which LANA maintains KSHV latency by targeting a major downstream effector of the Notch signaling pathway.
Receptor-Induced Conformational Changes in the SU Subunit of the Avian Sarcoma/Leukosis Virus A Envelope Protein: Implications for Fusion Activation
Authors: Delos Sue E. , Godby Jesse A. , White Judith M. 
Published: February 2005

ABSTRACT

The avian sarcoma/leukosis virus (ASLV) is activated for fusion by a two-step mechanism. For ASLV subgroup A (ASLV-A), association with its receptor (Tva) at neutral pH converts virions to a form that can bind target membranes and, in some assays, induce the lipid-mixing stage of fusion. Low pH is necessary to complete the fusion reaction. ASLV-A env (EnvA) exists on the viral surface as a trimer of heterodimers consisting of receptor binding (SU-A) and fusion-mediating (TM-A) subunits. As the receptor binding and fusion-mediating functions reside in separate subunits, we hypothesize that SU-A and TM-A are conformationally coupled. To begin to understand the effect of the binding of a soluble 47-residue domain of the receptor (sTva) on this coupling and the subsequent function of low pH, we prepared recombinant proteins representing full-length SU-A and a nested set of deletion mutant proteins. Full-length SU-A binds sTva with high affinity, but even small deletions at either the N or the C terminus severely impair sTva binding. We have purified the full-length SU-A subunit and characterized its interactions with sTva and the subsequent effect of low pH on the complex. sTva binds SU-A with an apparent

K
D

of 3 pM. Complex formation occludes hydrophobic surfaces and tryptophan residues and leads to a partial loss of α-helical structure in SU-A. Low pH does not alter the off rate for the complex, further alter the secondary structure of SU-A, or induce measurable changes in tryptophan environment. The implications of these findings for fusion are discussed.
Stoichiometry of Antibody Neutralization of Human Immunodeficiency Virus Type 1
Authors: Yang Xinzhen , Kurteva Svetla , Lee Sandra , Sodroski Joseph 
Published: February 2005

ABSTRACTThe human immunodeficiency virus envelope glycoproteins function as trimers on the viral surface, where they are targeted by neutralizing antibodies. Different monoclonal antibodies neutralize human immunodeficiency virus type 1 (HIV-1) infectivity by binding to structurally and functionally distinct moieties on the envelope glycoprotein trimer. By measuring antibody neutralization of viruses with mixtures of neutralization-sensitive and neutralization-resistant envelope glycoproteins, we demonstrate that the HIV-1 envelope glycoprotein trimer is inactivated by the binding of a single antibody molecule. Virus neutralization requires essentially all of the functional trimers to be occupied by at least one antibody. This model applies to antibodies differing in neutralizing potency and to virus isolates with various neutralization sensitivities. Understanding these requirements for HIV-1 neutralization by antibodies will assist in establishing goals for an effective AIDS vaccine.
The Cytokine Osteopontin Modulates the Severity of Rotavirus Diarrhea
Authors: Rollo Ellen E. , Hempson Scott J. , Bansal Ajay , Tsao Ernest , Habib Iman , Rittling Susan R. , Denhardt David T. , Mackow Erich R. , Shaw Robert D. 
Published: February 2005

ABSTRACTOsteopontin (OPN) is a sialated phosphoprotein found in tissues and secreted into body fluids. It is an integrin ligand with pleiotropic functions as an extracellular matrix protein in mineralized tissues and a cytokine that is active in cell signaling (A. B. Tuck, C. Hota, S. M. Wilson, and A. F. Chambers, Oncogene22:1198-1205, 2003). To determine whether OPN may be important in mucosal defense against viral pathogens, we evaluated the OPN response to rotavirus infection and the extent of diarrhea manifested by infectedopnnull mutant (opn−/−) mice. Reverse transcription-PCR, Northern and Western blots, and immunohistochemical studies of the HT-29 intestinal epithelial cell line and murine intestine were used to evaluate OPN mRNA and product. Intestinal closed loops and diarrheal observations determined disease severity and duration. OPN mRNA levels increased after infection of HT-29 cells, peaking in 4 to 6 h. Infected cultures contained 925 μg of OPN/ml, while for controls the levels were below detection (50 μg/ml). Infection increased OPN mRNA levels in intestinal tissue between 2 and 24 h postinoculation and increased OPN protein in intestinal fluid. The cellular localization of OPN was supranuclear and apical, and responding cells were diffusely distributed on the villus surface. Three days after infection, closed intestinal loops fromopn−/−mice contained more fluid than loops from controls, although secretion levels at the onset of illness were similar. Null mutant mice experienced more intense and prolonged diarrhea than controls. Rotavirus infection of intestinal epithelial cells and murine intestine caused marked increases in OPN mRNA levels and secreted OPN protein. OPN-deficient mice suffered prolonged disease.