bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patterns of Susceptibility of
Aspergillus
Isolates Recovered from Patients Enrolled in the Transplant-Associated Infection Surveillance Network
Authors: Baddley John W. , Marr Kieren A. , Andes David R. , Walsh Thomas J. , Kauffman Carol A. , Kontoyiannis Dimitrios P. , Ito James I. , Balajee S. Arunmozhi , Pappas Peter G. , Moser Stephen A. 
Published: August 2009

ABSTRACT

We analyzed antifungal susceptibilities of 274 clinical
Aspergillus
isolates from transplant recipients with proven or probable invasive aspergillosis collected as part of the Transplant-Associated Infection Surveillance Network (TRANSNET) and examined the relationship between MIC and mortality at 6 or 12 weeks. Antifungal susceptibility testing was performed by the Clinical and Laboratory Standards Institute (CLSI) M38-A2 broth dilution method for amphotericin B (AMB), itraconazole (ITR), voriconazole (VOR), posaconazole (POS), and ravuconazole (RAV). The isolate collection included 181
Aspergillus fumigatus
, 28
Aspergillus niger
, 27
Aspergillus flavus
, 22
Aspergillus terreus
, seven
Aspergillus versicolor
, five
Aspergillus calidoustus
, and two
Aspergillus nidulans
isolates and two isolates identified as
Aspergillus
spp. Triazole susceptibilities were ≤4 μg/ml for most isolates (POS, 97.6%; ITR, 96.3%; VOR, 95.9%; RAV, 93.5%). The triazoles were not active against the five
A. calidoustus
isolates, for which MICs were ≥4 μg/ml. AMB inhibited 93.3% of isolates at an MIC of ≤1 μg/ml. The exception was
A. terreus
, for which 15 (68%) of 22 isolates had MICs of >1 μg/ml. One of 181 isolates of
A. fumigatus
showed resistance (MIC ≥ 4 μg/ml) to two of three azoles tested. Although there appeared to be a correlation of higher VOR MICs with increased mortality at 6 weeks, the relationship was not statistically significant (
R
2
= 0.61;
P
= 0.065). Significant relationships of in vitro MIC to all-cause mortality at 6 and 12 weeks for VOR or AMB were not found.
Recurrent
Klebsiella pneumoniae
Liver Abscess: Clinical and Microbiological Characteristics
Authors: Yang Ya-Sung , Siu L. K. , Yeh Kuo-Ming , Fung Chang-Phong , Huang Shenq-Jie , Hung Han-Chang , Lin Jung-Chung , Chang Feng-Yee 
Published: August 2009

ABSTRACT

Recurrent
Klebsiella pneumoniae
liver abscesses (KLAs) are rarely reported. Six cases of recurrent KLAs are characterized. Most of the patients had diabetes and K1 serotype KLAs. All of the isolates were uniformly susceptible to cefazolin. Distinct molecular fingerprints were found for the strains isolated from both primary and recurrent KLAs.
Rapid Human Immunodeficiency Virus Test Quality Assurance Practices and Outcomes among Testing Sites Affiliated with 17 Public Health Departments
Authors: Wesolowski Laura G. , Ethridge Steven F. , Martin Eugene G. , Cadoff Evan M. , MacKellar Duncan A. 
Published: August 2009

ABSTRACT

Rapid human immunodeficiency virus testing is often conducted in nonclinical settings by staff with limited training, so quality assurance (QA) monitoring is critical to ensure accuracy of test results. Rapid tests (
n
= 86,749) were generally conducted according to manufacturers' instructions, but ongoing testing competency assessments and on-site QA monitoring were not uniformly conducted.
Occurrence of OXA-107 and IS
Aba
1 in Carbapenem-Resistant Isolates of
Acinetobacter baumannii
from Croatia
Authors: Goic-Barisic Ivana , Bedenic Branka , Tonkic Marija , Novak Anita , Katic Stjepan , Kalenic Smilja , Punda-Polic Volga , Towner Kevin J. 
Published: August 2009

ABSTRACT

Carbapenem-resistant isolates of
Acinetobacter baumannii
from intensive care units at Split University Hospital, Split, Croatia, were studied. Most (100 of 106) had IS
Aba
1 inserted upstream of a
bla
OXA-107
gene, encoding an unusual OXA-51-type oxacillinase. Pulsed-field gel electrophoresis revealed that the isolates formed three clusters belonging to the sequence group 2 (European clone 1) lineage.
X4 Human Immunodeficiency Virus Type 1 gp120 Down-Modulates Expression and Immunogenicity of Codelivered Antigens
Authors: Hovav Avi-Hai , Santosuosso Michael , Bivas-Benita Maytal , Plair Andre , Cheng Alex , Elnekave Mazal , Righi Elda , Chen Tao , Kashiwagi Satoshi , Panas Michael W. , Xiang Shi-Hua , Furmanov Karina , Letvin Norman L. , Poznansky Mark C. 
Published: August 2009

ABSTRACT
In order to increase the immune breadth of human immunodeficiency virus (HIV) vaccines, strategies such as immunization with several HIV antigens or centralized immunogens have been examined. HIV-1 gp120 protein is a major immunogen of HIV and has been routinely considered for inclusion in both present and future AIDS vaccines. However, recent studies proposed that gp120 interferes with the generation of immune response to codelivered antigens. Here, we investigate whether coimmunization with plasmid-encoded gp120 alters the immune response to other coadministered plasmid encoded antigens such as luciferase or ovalbumin in a mouse model. We found that the presence of gp120 leads to a significant reduction in the expression level of the codelivered antigen in vivo. Antigen presentation by antigen-presenting cells was also reduced and resulted in the induction of weak antigen-specific cellular and humoral immune responses. Importantly, gp120-mediated immune interference was observed after administration of the plasmids at the same or at distinct locations. To characterize the region in gp120 mediating these effects, we used plasmid constructs encoding gp120 that lacks the V1V2 loops (ΔV1V2) or the V3 loop (ΔV3). After immunization, the ΔV1V2, but not the ΔV3 construct, was able to reduce antigen expression, antigen presentation, and subsequently the immunogenicity of the codelivered antigen. The V3 loop dependence of this phenomenon seems to be limited to V3 loops known to interact with the CXCR4 molecule but not with CCR5. Our study presents a novel mechanism by which HIV-1 gp120 interferes with the immune response against coadministered antigen in a polyvalent vaccine preparation.
Characterization of a Mumps Virus Nucleocapsidlike Particle
Authors: Cox Robert , Green Todd J. , Qiu Shihong , Kang Jungsoon , Tsao Jun , Prevelige Peter E. , He Biao , Luo Ming 
Published: August 2009

ABSTRACT

The nucleocapsid protein (NP) of mumps virus (MuV), a paramyxovirus, was coexpressed with the phosphoprotein (P) in
Escherichia coli
. The NP and P proteins form a soluble complex containing RNA. Under a transmission electron microscope, the NP-RNA complex appears as a nucleocapsidlike ring that has a diameter of approximately 20 nm with 13 subunits. There is a piece of single-stranded RNA with a length of 78 nucleotides in the NP-RNA ring. Shorter RNA pieces are also visible. The MuV NP protein may provide weaker protection of the RNA than the NP protein of some other negative-strand RNA viruses, reflecting the degree of NP protein association.
Human Uterine Natural Killer Cells but Not Blood Natural Killer Cells Inhibit Human Immunodeficiency Virus Type 1 Infection by Secretion of CXCL12
Authors: Mselle Teddy F. , Howell Alexandra L. , Ghosh Mimi , Wira Charles R. , Sentman Charles L. 
Published: August 2009

ABSTRACTNatural killer (NK) cells derived from the human female reproductive tract (FRT) are phenotypically and functionally distinct from those obtained from peripheral blood. Because the FRT is a primary site of human immunodeficiency virus type 1 (HIV-1) infection in women, we determined whether soluble factors secreted by uterine-derived NK (uNK) cells inhibit HIV-1 infection. Clonal populations of uNK cells were activated with interleukin-12 (IL-12) and IL-15, and conditioned media (CM) from these cultures evaluated for their ability to inhibit infection of cells by HIV-1IIIB, HIV-1NL4.3, and HIV-1HC4(X4-tropic) or HIV-1BaL(R5-tropic) viruses. We found that soluble factors secreted by activated uNK cells significantly inhibited X4-tropic virus infection of TZM-bl cells, peripheral blood mononuclear cells, and primary human endometrial cells, but not infection by HIV-1BaL. In contrast, CM from peripheral blood NK (bNK) cells did not inhibit HIV-1 infection of cells. Analysis of factors secreted from uNK clones with anti-HIV-1 activity demonstrated significantly higher levels of CXCL12 compared to uNK clones without this activity, and the HIV inhibitory activity was neutralized by antibodies to CXCL12. Collectively, these data demonstrate that human uNK cells release chemokines with anti-HIV-1 activity for X4-tropic strains and this suggest that these chemokines may contribute to the inhibition of X4-tropic strain transmission across mucosal tissues.
Virion-Associated Vpr of Human Immunodeficiency Virus Type 1 Triggers Activation of Apoptotic Events and Enhances Fas-Induced Apoptosis in Human T Cells
Authors: Arokium Hubert , Kamata Masakazu , Chen Irvin 
Published: August 2009

ABSTRACTHuman immunodeficiency virus type 1 (HIV-1) Vpr protein exists in three different forms: soluble, intracellular, and virion associated. Previous studies showed that virion-associated Vpr induces apoptosis in activated peripheral blood mononuclear cells (PBMCs) and Jurkat T cells, but these studies were conducted in the presence of other de novo-expressed HIV proteins that may have had additive proapoptotic effects. In this report, we show that virion-associated Vpr triggers apoptosis through caspases 3/7 and 9 in human T cells independently of other HIV de novo-expressed proteins. In contrast to a previous study, we also detected the activation of caspase 8, the initiator caspase of the death receptor pathway. However, activation of all caspases by virion-associated Vpr was independent of the Fas death receptor pathway. Further analyses showed that virion-associated Vpr enhanced caspase activation in Fas-mediated apoptosis in Jurkat T cells and human activated PBMCs. Thus, our results indicate for the first time that viral particles that contain virion-associated Vpr can cause apoptosis in the absence of other de novo-expressed viral factors and can act in synergy with the Fas receptor pathway, thereby enhancing the apoptotic process in T cells. These findings suggest that virion-associated Vpr can contribute to the depletion of CD4+lymphocytes either directly or by enhancing Fas-mediated apoptosis during acute HIV-1 infection and in AIDS.
A Single-Amino-Acid Substitution in a Polymerase Protein of an H5N1 Influenza Virus Is Associated with Systemic Infection and Impaired T-Cell Activation in Mice
Authors: Fornek Jamie L. , Gillim-Ross Laura , Santos Celia , Carter Victoria , Ward Jerrold M. , Cheng Lily I. , Proll Sean , Katze Michael G. , Subbarao Kanta 
Published: August 2009

ABSTRACT
The transmission of H5N1 influenza viruses from birds to humans poses a significant public health threat. A substitution of glutamic acid for lysine at position 627 of the PB2 protein of H5N1 viruses has been identified as a virulence determinant. We utilized the BALB/c mouse model of H5N1 infection to examine how this substitution affects virus-host interactions and leads to systemic infection. Mice infected with H5N1 viruses containing lysine at amino acid 627 in the PB2 protein exhibited an increased severity of lesions in the lung parenchyma and the spleen, increased apoptosis in the lungs, and a decrease in oxygen saturation. Gene expression profiling revealed that T-cell receptor activation was impaired at 2 days postinfection (dpi) in the lungs of mice infected with these viruses. The inflammatory response was highly activated in the lungs of mice infected with these viruses and was sustained at 4 dpi. In the spleen, immune-related processes including NK cell cytotoxicity and antigen presentation were highly activated by 2 dpi. These differences are not attributable solely to differences in viral replication in the lungs but to an inefficient immune response early in infection as well. The timing and magnitude of the immune response to highly pathogenic influenza viruses is critical in determining the outcome of infection. The disruption of these factors by a single-amino-acid substitution in a polymerase protein of an influenza virus is associated with severe disease and correlates with the spread of the virus to extrapulmonary sites.
An Amphipathic α-Helix at the C Terminus of Hepatitis C Virus Nonstructural Protein 4B Mediates Membrane Association
Authors: Gouttenoire Jérôme , Montserret Roland , Kennel Audrey , Penin François , Moradpour Darius 
Published: August 2009

ABSTRACT
Nonstructural protein 4B (NS4B) plays an essential role in the formation of the hepatitis C virus (HCV) replication complex. It is an integral membrane protein that has been only poorly characterized to date. It is believed to comprise a cytosolic N-terminal part, a central part harboring four transmembrane passages, and a cytosolic C-terminal part. Here, we describe an amphipathic α-helix at the C terminus of NS4B (amino acid residues 229 to 253) that mediates membrane association and is involved in the formation of a functional HCV replication complex.
Mechanism of Human Immunodeficiency Virus Type 1 Resistance to Monoclonal Antibody b12 That Effectively Targets the Site of CD4 Attachment
Authors: Wu Xueling , Zhou Tongqing , O'Dell Sijy , Wyatt Richard T. , Kwong Peter D. , Mascola John R. 
Published: August 2009

ABSTRACT
The region of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 that engages its primary cellular receptor CD4 forms a site of vulnerability to neutralizing antibodies. The monoclonal antibody b12 exploits the conservation and accessibility of the CD4-binding site to neutralize many, though not all, HIV-1 isolates. To understand the basis of viral resistance to b12, we used the atomic-level definition of b12-gp120 contact sites to study a panel of diverse circulating viruses. A combination of sequence analysis, computational modeling, and site-directed mutagenesis was used to determine the influence of amino acid variants on binding and neutralization by b12. We found that several substitutions within the dominant b12 contact surface, called the CD4-binding loop, mediated b12 resistance, and that these substitutions resided just proximal to the known CD4 contact surface. Hence, viruses varied in key b12 contact residues that are proximal to, but not part of, the CD4 contact surface. This explained how viral isolates were able to evade b12 neutralization while maintaining functional binding to CD4. In addition, some viruses were resistant to b12 despite minimal sequence variation at b12 contact sites. Such neutralization resistance usually could be reversed by alterations at residues thought to influence the quaternary configuration of the viral envelope spike. To design immunogens that elicit neutralizing antibodies directed to the CD4-binding site, researchers need to address the antigenic variation within this region of gp120 and the restricted access to the CD4-binding site imposed by the native configuration of the trimeric viral envelope spike.
Race between Retroviral Spread and CD4+T-Cell Response Determines the Outcome of Acute Friend Virus Infection
Authors: Pike Rebecca , Filby Andrew , Ploquin Mickaël J.-Y. , Eksmond Urszula , Marques Rute , Antunes Inês , Hasenkrug Kim , Kassiotis George 
Published: August 2009

ABSTRACTRetroviruses can establish persistent infection despite induction of a multipartite antiviral immune response. Whether collective failure of all parts of the immune response or selective deficiency in one crucial part underlies the inability of the host to clear retroviral infections is currently uncertain. We examine here the contribution of virus-specific CD4+T cells in resistance against Friend virus (FV) infection in the murine host. We show that the magnitude and duration of the FV-specific CD4+T-cell response is directly proportional to resistance against acute FV infection and subsequent disease. Notably, significant protection against FV-induced disease is afforded by FV-specific CD4+T cells in the absence of a virus-specific CD8+T-cell or B-cell response. Enhanced spread of FV infection in hosts with increased genetic susceptibility or coinfection with Lactate dehydrogenase-elevating virus (LDV) causes a proportional increase in the number of FV-specific CD4+T cells required to control FV-induced disease. Furthermore, ultimate failure of FV/LDV coinfected hosts to control FV-induced disease is accompanied by accelerated contraction of the FV-specific CD4+T-cell response. Conversely, an increased frequency or continuous supply of FV-specific CD4+T cells is both necessary and sufficient to effectively contain acute infection and prevent disease, even in the presence of coinfection. Thus, these results suggest that FV-specific CD4+T cells provide significant direct protection against acute FV infection, the extent of which critically depends on the ratio of FV-infected cells to FV-specific CD4+T cells.
Adaptive Mutations in a Human Immunodeficiency Virus Type 1 Envelope Protein with a Truncated V3 Loop Restore Function by Improving Interactions with CD4
Authors: Agrawal-Gamse Caroline , Lee Fang-Hua , Haggarty Beth , Jordan Andrea P. O. , Yi Yanjie , Lee Benhur , Collman Ronald G. , Hoxie James A. , Doms Robert W. , Laakso Meg M. 
Published: August 2009

ABSTRACT
We previously reported that a human immunodeficiency virus type 1 (HIV-1) clade B envelope protein with a severely truncated V3 loop regained function after passage in tissue culture. The adapted virus, termed TA1, retained the V3 truncation, was exquisitely sensitive to neutralization by the CD4 binding site monoclonal antibody b12 and by HIV-positive human sera, used CCR5 to enter cells, and was completely resistant to small molecule CCR5 antagonists. To examine the mechanistic basis for these properties, we singly and in combination introduced each of the 5 mutations from the adapted clone TA1 into the unadapted envelope. We found that single amino acid changes in the C3 region, the V3 loop, and in the fusion peptide were responsible for imparting near-normal levels of envelope function to TA1. T342A, which resulted in the loss of a highly conserved glycosylation site in C3, played the primary role. The adaptive amino acid changes had no impact on CCR5 antagonist resistance but made virus more sensitive to neutralization by antibodies to the CD4 binding site, modestly enhanced affinity for CD4, and made TA1 more responsive to CD4 binding. Specifically, TA1 was triggered by soluble CD4 more readily than the parental Env and, unlike the parental Env, could mediate entry on cells that express low levels of CD4. In contrast, TA1 interacted with CCR5 less efficiently and was highly sensitive to antibodies that bind to the CCR5 N terminus and ECL2. Therefore, enhanced utilization of CD4 is one mechanism by which HIV-1 can overcome mutations in the V3 region that negatively affect CCR5 interactions.
A Quantitative Affinity-Profiling System That Reveals Distinct CD4/CCR5 Usage Patterns among Human Immunodeficiency Virus Type 1 and Simian Immunodeficiency Virus Strains
Authors: Johnston Samantha. H. , Lobritz Michael A. , Nguyen Sandra , Lassen Kara , Delair Shirley , Posta Filippo , Bryson Yvonne J. , Arts Eric J. , Chou Tom , Lee Benhur 
Published: August 2009

ABSTRACT
The affinity of human immunodeficiency virus (HIV) envelope for CD4 and CCR5 appears to be associated with aspects of R5 virus (virus using the CCR5 coreceptor) pathogenicity. However, entry efficiency results from complex interactions between the viral envelope glycoprotein and both CD4 and CCR5, which limits attempts to correlate viral pathogenicity with surrogate measures of envelope CD4 and CCR5 affinities. Here, we present a system that provides a quantitative and comprehensive characterization of viral entry efficiency as a direct interdependent function of both CD4 and CCR5 levels. This receptor affinity profiling system also revealed heretofore unappreciated complexities underlying CD4/CCR5 usage. We first developed a dually inducible cell line in which CD4 and CCR5 could be simultaneously and independently regulated within a physiologic range of surface expression. Infection by multiple HIV type 1 (HIV-1) and simian immunodeficiency virus isolates could be examined simultaneously for up to 48 different combinations of CD4/CCR5 expression levels, resulting in a distinct usage pattern for each virus. Thus, each virus generated a unique three-dimensional surface plot in which viral infectivity varied as a function of both CD4 and CCR5 expression. From this functional form, we obtained a sensitivity vector along with corresponding metrics that quantified an isolate's overall efficiency of CD4/CCR5 usage. When applied to viral isolates with well-characterized sensitivities to entry/fusion inhibitors, the vector metrics were able to encapsulate their known biological phenotypes. The application of the vector metrics also indicated that envelopes derived from elite suppressors had overall-reduced entry efficiencies compared to those of envelopes derived from chronically infected viremic progressors. Our affinity-profiling system may help to refine studies of R5 virus tropism and pathogenesis.
Broad Neutralization of Human Immunodeficiency Virus Type 1 Mediated by Plasma Antibodies against the gp41 Membrane Proximal External Region
Authors: Gray Elin S. , Madiga Maphuti C. , Moore Penny L. , Mlisana Koleka , Abdool Karim Salim S. , Binley James M. , Shaw George M. , Mascola John R. , Morris Lynn 
Published: August 2009

ABSTRACT
We identified three cross-neutralizing plasma samples with high-titer anti-membrane proximal external region (MPER) peptide binding antibodies from among 156 chronically human immunodeficiency virus type 1-infected individuals. In order to establish if these antibodies were directly responsible for the observed neutralization breadth, we used MPER-coated magnetic beads to deplete plasmas of these specific antibodies. Depletion of anti-MPER antibodies from BB34, CAP206, and SAC21 resulted in 77%, 68%, and 46% decreases, respectively, in the number of viruses neutralized. Antibodies eluted from the beads showed neutralization profiles similar to those of the original plasmas, with potencies comparable to those of the known anti-MPER monoclonal antibodies (MAbs), 4E10, 2F5, and Z13e1. The anti-MPER neutralizing antibodies in BB34 were present in the immunoglobulin G3 subclass-enriched fraction. Alanine scanning of the MPER showed that the antibodies from these three plasmas had specificities distinct from those of the known MAbs, requiring one to three crucial residues at positions 670, 673, and 674. These data demonstrate the existence of MPER-specific cross-neutralizing antibodies in plasma, although the ability to elicit such potent antiviral antibodies during natural infection appears to be rare. Nevertheless, the identification of three novel antibody specificities within the MPER supports its further study as a promising target for vaccine design.