bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caspofungin Resistance inCandida albicans: Correlating Clinical Outcome with Laboratory Susceptibility Testing of Three Isogenic Isolates Serially Obtained from a Patient with Progressive Candida Esophagitis
Authors: Hernandez Steve , López-Ribot José L. , Najvar Laura K. , McCarthy Dora I. , Bocanegra Rosie , Graybill John R. 
Published: March 2004

ABSTRACTA patient with azole-refractory thrush-esophagitis responded initially to caspofungin, but the treatment eventually failed. In a murine model, caspofungin was effective against two early isolates for which the MICs of caspofungin were low, but it was less effective against a late isolate for which the MIC of caspofungin was greater. We concluded that there is a correlation between in vivo failure and rising in vitro caspofungin MICs.
Molecular Analysis of Metallo-β-Lactamase Gene
bla
SPM-1
-Surrounding Sequences from Disseminated
Pseudomonas aeruginosa
Isolates in Recife, Brazil
Authors: Poirel Laurent , Magalhaes Marcelo , Lopes Miguel , Nordmann Patrice 
Published: March 2004

ABSTRACT

The spread of clonally related carbapenem-resistant
Pseudomonas aeruginosa
producing the metallo-β-lactamase SPM-1 was found in Recife, Brazil. Upstream of
bla
SPM-1
, a novel common region (CR4) was identified, comprising an open reading frame,
orf495
, whose product shares significant identity with putative recombinases, such as Orf513. CR4 may be responsible for mobilization and expression of
bla
SPM-1
.
Macrolide Resistance Determinants of Invasive and Noninvasive Group B Streptococci in a Turkish Hospital
Authors: Acikgoz Ziya Cibali , Almayanlar Ebru , Gamberzade Sohret , Gocer Safiye 
Published: March 2004

ABSTRACT

Macrolide resistance in 156 consecutive group B streptococcal isolates was investigated. Thirty-five isolates (22.4%) had inducible (80%) or constitutive (20%) erythromycin resistance. The genes responsible were
erm
(B),
erm
(A) subclass
erm
(TR), and
erm
(B) plus
erm
(TR) in 62.9, 2.9, and 8.6% of isolates, respectively. Nine isolates (25.7%) harbored neither
mef
nor detectable
erm
genes.
Field Evaluation of a Novel Colorimetric Method—Double-Site Enzyme-Linked Lactate Dehydrogenase Immunodetection Assay—To Determine Drug Susceptibilities of
Plasmodium falciparum
Clinical Isolates from Northwestern Thailand
Authors: Brockman Alan , Singlam Sittaporn , Phiaphun Lucy , Looareesuwan Sornchai , White Nicholas J. , Nosten François 
Published: March 2004

ABSTRACT

A double-site enzyme-linked lactate dehydrogenase enzyme immunodetection assay was tested against field isolates of
Plasmodium falciparum
for assessing in vitro drug susceptibilities to a wide range of antimalarial drugs. Its sensitivity allowed the use of parasite densities as low as 200 parasites/μl of blood. Being a nonisotopic, colorimetric assay, it lies within the capabilities of a modest laboratory at the district level.
Repression of Tax Expression Is Associated both with Resistance of Human T-Cell Leukemia Virus Type 1-Infected T Cells to Killing by Tax-Specific Cytotoxic T Lymphocytes and with Impaired Tumorigenicity in a Rat Model
Authors: Nomura Machiko , Ohashi Takashi , Nishikawa Keiko , Nishitsuji Hironori , Kurihara Kiyoshi , Hasegawa Atsuhiko , Furuta Rika A. , Fujisawa Jun-ichi , Tanaka Yuetsu , Hanabuchi Shino , Harashima Nanae , Masuda Takao , Kannagi Mari 
Published: March 2004

ABSTRACTHuman T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL). Although the viral transactivation factor, Tax, has been known to have apparent transforming ability, the exact function of Tax in ATL development is still not clear. To understand the role of Tax in ATL development, we introduced short-interfering RNAs (siRNAs) against Tax in a rat HTLV-1-infected T-cell line. Our results demonstrated that expression of siRNA targeting Tax successfully downregulated Tax expression. Repression of Tax expression was associated with resistance of the HTLV-1-infected T cells to Tax-specific cytotoxic-T-lymphocyte killing. This may be due to the direct effect of decreased Tax expression, because the Tax siRNA did not alter the expression of MHC-I, CD80, or CD86. Furthermore, T cells with Tax downregulation appeared to lose the ability to develop tumors in T-cell-deficient nude rats, in which the parental HTLV-1-infected cells induce ATL-like lymphoproliferative disease. These results indicated the importance of Tax both for activating host immune response against the virus and for maintaining the growth ability of infected cells in vivo. Our results provide insights into the mechanisms how the host immune system can survey and inhibit the growth of HTLV-1-infected cells during the long latent period before the onset of ATL.
Human T-Cell Lymphotropic Virus Type 1 Open Reading Frame II-Encoded p30
II
Is Required for In Vivo Replication: Evidence of In Vivo Reversion
Authors: Silverman Lee R. , Phipps Andrew J. , Montgomery Andrew , Ratner Lee , Lairmore Michael D. 
Published: March 2004

ABSTRACT

Human T-cell lymphotropic virus type 1 (HTLV-1) causes adult T-cell leukemia/lymphoma and exhibits high genetic stability in vivo. HTLV-1 contains four open reading frames (ORFs) in its pX region. ORF II encodes two proteins, p30
II
and p13
II
, both of which are incompletely characterized. p30
II
localizes to the nucleus or nucleolus and has distant homology to the transcription factors Oct-1, Pit-1, and POU-M1. In vitro studies have demonstrated that at low concentrations, p30
II
differentially regulates cellular and viral promoters through an interaction with CREB binding protein/p300. To determine the in vivo significance of p30
II
, we inoculated rabbits with cell lines expressing either a wild-type clone of HTLV-1 (ACH.1) or a clone containing a mutation in ORF II, which eliminated wild-type p30
II
expression (ACH.30.1). ACH.1-inoculated rabbits maintained higher HTLV-1-specific antibody titers than ACH.30.1-inoculated rabbits, and all ACH.1-inoculated rabbits were seropositive for HTLV-1, whereas only two of six ACH.30.1-inoculated rabbits were seropositive. Provirus could be consistently PCR amplified from peripheral blood mononuclear cell (PBMC) DNA in all ACH.1-inoculated rabbits but in only three of six ACH.30.1-inoculated rabbits. Quantitative competitive PCR indicated higher PBMC proviral loads in ACH.1-inoculated rabbits. Interestingly, sequencing of ORF II from PBMC of provirus-positive ACH.30.1-inoculated rabbits revealed a reversion to wild-type sequence with evidence of early coexistence of mutant and wild-type sequence. Our data provide evidence that HTLV-1 must maintain its key accessory genes to survive in vivo and that in vivo pressures select for maintenance of wild-type ORF II gene products during the early course of infection.
Interplay between Alpha/Beta and Gamma Interferons with B, T, and Natural Killer Cells in the Defense against Herpes Simplex Virus Type 1
Authors: Vollstedt Sabine , Arnold Susi , Schwerdel Cornelia , Franchini Marco , Alber Gottfried , Di Santo James P. , Ackermann Mathias , Suter Mark 
Published: March 2004

ABSTRACTThe essential components of the immune system that control primary and chronic infection with herpes simplex virus type 1 (HSV-1) in mice were investigated. Infection within the first few days can be controlled by alpha/beta interferon (IFN-α/β) alone without significant contribution of B, T, or NK cells. IFN-α/β and IFN-γ cooperate in the elimination of virus in the absence of these lymphocytes. In contrast, B, T, or NK cells appear to be required to control persistent infection with HSV-1. These results suggest that distinct and essential immune elements are recruited in a time-dependent fashion to control acute and persistent HSV-1 infection.
Defective RNA Replication and Late Gene Expression in Temperature-Sensitive Influenza Viruses Expressing Deleted Forms of the NS1 Protein
Authors: Falcón Ana M. , Marión Rosa M. , Zürcher Thomas , Gómez Paulino , Portela Agustín , Nieto Amelia , Ortín Juan 
Published: March 2004

ABSTRACT
Influenza A virus mutants expressing C-terminally deleted forms of the NS1 protein (NS1-81 and NS1-110) were generated by plasmid rescue. These viruses were temperature sensitive and showed a small plaque size at the permissive temperature. The accumulation of virion RNA in mutant virus-infected cells was reduced at the restrictive temperature, while the accumulation of cRNA or mRNA was not affected, indicating that the NS1 protein is involved in the control of transcription versus replication processes in the infection. The synthesis and accumulation of late virus proteins were reduced in NS1-81 mutant-infected cells at the permissive temperature and were essentially abolished for both viruses at the restrictive temperature, while synthesis and accumulation of nucleoprotein (NP) were unaffected. Probably as a consequence, the nucleocytoplasmic export of virus NP was strongly inhibited at the restrictive temperature. These results indicate that the NS1 protein is essential for nuclear and cytoplasmic steps during the virus cycle.
Poly(A)- and Primer-Independent RNA Polymerase of
Norovirus
Authors: Fukushi Shuetsu , Kojima Shigeyuki , Takai Reiko , Hoshino Fuminori B. , Oka Tomoichiro , Takeda Naokazu , Katayama Kazuhiko , Kageyama Tsutomu 
Published: March 2004

ABSTRACT

Replication of positive-strand caliciviruses is mediated by a virus-encoded RNA-dependent RNA polymerase (RdRp). To study the replication of
Norovirus
(NV), a member of the family
Caliciviridae
, we used a recombinant baculovirus system to express an enzymatically active RdRp protein from the 3D region of the NV genome and defined conditions for optimum enzymatic activity. Using an RNA template from the NV 3′ genomic region, we observed similar levels of enzymatic activity in assays with and without a poly(A) tail. RdRp activity was not significantly affected by the addition of an RNA primer to the reaction mixture. Thus, the NV RdRp exhibited primer- and poly(A)-independent RNA polymerase activity. While the RdRp inhibitor phosphonoacetic acid inhibited NV RdRp activity, another gliotoxin did not. The active recombinant NV RdRp will be of benefit to studies of NV replication and will facilitate the development of specific inhibitors of NV proliferation.
Membrane Cofactor Protein Is a Receptor for Adenoviruses Associated with Epidemic Keratoconjunctivitis
Authors: Wu Eugene , Trauger Sunia A. , Pache Lars , Mullen Tina-Marie , Von Seggern Daniel J. , Siuzdak Gary , Nemerow Glen R. 
Published: March 2004

ABSTRACTSubgroup D adenovirus (Ad) types 8, 19, and 37 (Ad8, -19, and -37, respectively) are causative agents of epidemic keratoconjunctivitis and genital tract infections. Previous studies showed that Ad37 binds to a 50-kDa membrane glycoprotein expressed on human ocular (conjunctival) cells. To identify and characterize the role of the 50-kDa glycoprotein in Ad37 infection, we partially purified this molecule from solubilized Chang C conjunctival cell membranes by using lentil lectin chromatography and preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Liquid chromatography coupled to nano-electrospray ionization-tandem mass spectrometry was subsequently used to identify four Ad37 receptor candidates: CD46, CD87, CD98, and CD147. Immunodepletion analyses demonstrated that the 50-kDa protein is identical to CD46 (also known as membrane cofactor protein). The Ad37, but not Ad5, fiber knob bound to the extracellular domain of CD46, demonstrating a direct interaction of an Ad37 capsid protein with CD46. An antibody specific for the N-terminal 19 amino acids of CD46 also blocked Ad37 infection of human cervical carcinoma and conjunctival cells, indicating a requirement for CD46 in infection. Finally, expression of a 50-kDa isoform of human CD46 in a CD46-null cell line increased cell binding by wild-type Ad37 and gene delivery by an Ad vector pseudotyped with the Ad37 fiber, but not by a vector bearing the Ad5 fiber. Together, these studies demonstrate that CD46 serves as an attachment receptor for Ad37 and shed further light on the cell entry pathway of subgroup D Ads.
Highly Effective Control of an AIDS Virus Challenge in Macaques by Using Vesicular Stomatitis Virus and Modified Vaccinia Virus Ankara Vaccine Vectors in a Single-Boost Protocol
Authors: Ramsburg Elizabeth , Rose Nina F. , Marx Preston A. , Mefford Megan , Nixon Douglas F. , Moretto Walter J. , Montefiori David , Earl Patricia , Moss Bernard , Rose John K. 
Published: March 2004

ABSTRACT

Previous studies have shown that vaccination and boosting of rhesus macaques with attenuated vesicular stomatitis virus (VSV) vectors encoding Env and Gag proteins of simian immunodeficiency virus-human immunodeficiency virus (SHIV) hybrid viruses protect rhesus macaques from AIDS after challenge with the highly pathogenic SHIV 89.6P (23). In the present study, we compared the effectiveness of a single prime-boost protocol consisting of VSV vectors expressing SHIV Env, Gag, and Pol proteins to that of a protocol consisting of a VSV vector prime followed with a single boost with modified vaccinia virus Ankara (MVA) expressing the same SHIV proteins. After challenge with SHIV 89.6P, MVA-boosted animals controlled peak challenge viral loads to less than 2 × 10
6
copies/ml (a level significantly lower than that seen with VSV-boosted animals and lower than those reported for other vaccine studies employing the same challenge). MVA-boosted animals have shown excellent preservation of CD4
+
T cells, while two of four VSV-boosted animals have shown significant loss of CD4
+
T cells. The improved protection in MVA-boosted animals correlates with trends toward stronger prechallenge CD8
+
-T-cell responses to SHIV antigens and stronger postchallenge SHIV-neutralizing antibody production.
Recombinant Modified Vaccinia Virus Ankara Expressing a Soluble Form of Glycoprotein B Causes Durable Immunity and Neutralizing Antibodies against Multiple Strains of Human Cytomegalovirus
Authors: Wang Zhongde , La Rosa Corinna , Maas Rebecca , Ly Heang , Brewer John , Mekhoubad Shahram , Daftarian Pirouz , Longmate Jeff , Britt William J. , Diamond Don J. 
Published: March 2004

ABSTRACTHuman cytomegalovirus (CMV) is a viral pathogen that infects both genders, who remain asymptomatic unless they receive immunosuppressive drugs or acquire infections that cause reactivation of latent virus. CMV infection also causes serious birth defects following primary maternal infection during gestation. A safe and effective vaccine to limit disease in this population continues to be elusive. A well-studied antigen is glycoprotein B (gB), which is the principal target of neutralizing antibodies (NAb) towards CMV in humans and has been implicated as the viral partner in the receptor-mediated infection by CMV in a variety of cell types. Antibody-mediated virus neutralization has been proposed as a mechanism by which host immunity could modify primary infection. Towards this goal, an attenuated poxvirus, modified vaccinia virus Ankara (MVA), has been constructed to express soluble CMV gB (gB680-MVA) to induce CMV NAb. Very high levels of gB-specific CMV NAb were produced after two doses of the viral vaccine. NAb were durable within a twofold range for up to 6 months. Neutralization titers developed in immunized mice are equivalent to titers found clinically after natural infection. This viral vaccine, expressing gB derived from CMV strain AD169, induced antibodies that neutralized CMV strains of three different genotypes. Remarkably, preexisting MVA and vaccinia virus (poxvirus) immunity did not interfere with subsequent immunizations of gB680-MVA. The safety characteristics of MVA, combined with the robust immune response to CMV gB, suggest that this approach could be rapidly translated into the clinic.
Spread of Hepatitis B Viruses In Vitro Requires Extracellular Progeny and May Be Codetermined by Polarized Egress
Authors: Funk A. , Hohenberg H. , Mhamdi M. , Will H. , Sirma H. 
Published: March 2004

ABSTRACT
Viruses can spread by different mechanisms: via intracellular particles through cell junctions to neighboring cells or via secreted virions to adjacent or remote cells. The observation of clusters of hepadnavirus-infected cells both in vivo and in primary hepatocytes neither proves the first mechanism nor excludes the second. In order to test which mechanism, if not both, is used by hepatitis B viruses in order to spread, we used primary duck hepatocytes and duck hepatitis B virus (DHBV) as an infection model. If extracellular progeny virus alone determines spreading, neutralizing antisera or drugs blocking virus binding to hepatocytes should abolish secondary infection. In order to test this, we used DHBV envelope-specific neutralizing antisera, as well as suramin, a known inhibitor of infection. Both reagents strongly reduced hepatocellular attachment of viral particles and almost completely abolished primary infection, whereas an ongoing intracellular infection was not affected as long as no progeny virus was released. In contrast, incubation of infected primary hepatocytes with these reagents during release of progeny virus completely prevented secondary infection. Moreover, the combination of electron and immunofluorescence microscopy analyses revealed the residence of viral particles in cytoplasmic vesicles preferentially located near the basolateral membrane of infected hepatocytes. Taken together, these data strongly suggest that hepatitis B viruses mainly spread by secreted, extracellular progeny and point to polarized egress of viral particles into intercellular compartments, which restricts their diffusion and favors transmission of virus to adjacent cells.
Epstein-Barr Virus Nuclear Antigen Leader Protein Induces Expression of Thymus- and Activation-Regulated Chemokine in B Cells
Authors: Kanamori Mikiko , Watanabe Shinya , Honma Reiko , Kuroda Masayuki , Imai Shosuke , Takada Kenzo , Yamamoto Naoki , Nishiyama Yukihiro , Kawaguchi Yasushi 
Published: March 2004

ABSTRACTEpstein-Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) plays a critical role in transformation of primary B lymphocytes to continuously proliferating lymphoblastoid cell lines (LCLs). To identify cellular genes in B cells whose expression is regulated by EBNA-LP, we performed microarray expression profiling on an EBV-negative human B-cell line, BJAB cells, that were transduced by a retroviral vector expressing the EBV EBNA-LP (BJAB-LP cells) and on BJAB cells that were transduced with a control vector (BJAB-vec cells). Microarray analysis led to the identification of a cellular gene encoding the CC chemokine TARC as a novel target gene that was induced by EBNA-LP. The levels of TARC mRNA expression and TARC secretion were significantly up-regulated in BJAB-LP compared with BJAB-vec cells. Induction of TARC was also observed when a subline of BJAB cells was converted by a recombinant EBV. Among the EBV-infected B-cell lines with the latency III phenotype that were tested, the LCLs especially secreted significantly high levels of TARC. The level of TARC secretion appeared to correlate with the level of full-length EBNA-LP expression. These results indicate that EBV infection induces TARC expression in B cells and that EBNA-LP is one of the viral gene products responsible for the induction.
Purified Recombinant Bluetongue Virus VP1 Exhibits RNA Replicase Activity
Authors: Boyce Mark , Wehrfritz Josa , Noad Rob , Roy Polly 
Published: March 2004

ABSTRACT

The polymerase protein of all known double-stranded RNA (dsRNA) viruses is located within a complex subviral core particle that is responsible for transcription of the viral genome. For members of the family
Reoviridae
, this particle allows messenger sense RNA synthesis while sequestering the viral genome away from cellular dsRNA surveillance systems during infection of eukaryotic cells. The core particle of bluetongue virus (BTV) consists of the major structural proteins VP3 and VP7 and the minor enzymatic proteins VP1 (polymerase), VP4 (capping enzyme), and VP6 (helicase). In this report we have characterized fully processive dsRNA synthesis by VP1 from a viral plus-strand RNA template in the absence of the other proteins of the BTV core. This replicase activity consists of de novo initiation of synthesis, followed by elongation of the minus strand. Purified VP1 exhibits little sequence specificity for BTV plus-strand template, suggesting that the choice of viral over nonviral RNA template comes from its association with other proteins within the viral core.
tRNA-Like Structure Regulates Translation of Brome Mosaic Virus RNA
Authors: Barends Sharief , Rudinger-Thirion Joëlle , Florentz Catherine , Giegé Richard , Pleij Cornelis W. A. , Kraal Barend 
Published: March 2004

ABSTRACT

For various groups of plant viruses, the genomic RNAs end with a tRNA-like structure (TLS) instead of the 3′ poly(A) tail of common mRNAs. The actual function of these TLSs has long been enigmatic. Recently, however, it became clear that for turnip yellow mosaic virus, a tymovirus, the valylated TLS
TYMV
of the single genomic RNA functions as a bait for host ribosomes and directs them to the internal initiation site of translation (with N-terminal valine) of the second open reading frame for the polyprotein. This discovery prompted us to investigate whether the much larger TLSs of a different genus of viruses have a comparable function in translation. Brome mosaic virus (BMV), a bromovirus, has a tripartite RNA genome with a subgenomic RNA4 for coat protein expression. All four RNAs carry a highly conserved and bulky 3′ TLS
BMV
(about 200 nucleotides) with determinants for tyrosylation. We discovered TLS
BMV
-catalyzed self-tyrosylation of the tyrosyl-tRNA synthetase but could not clearly detect tyrosine incorporation into any virus-encoded protein. We established that BMV proteins do not need TLS
BMV
tyrosylation for their initiation. However, disruption of the TLSs strongly reduced the translation of genomic RNA1, RNA2, and less strongly, RNA3, whereas coat protein expression from RNA4 remained unaffected. This aberrant translation could be partially restored by providing the TLS
BMV
in
trans
. Intriguingly, a subdomain of the TLS
BMV
could even almost fully restore translation to the original pattern. We discuss here a model with a central and dominant role for the TLS
BMV
during the BMV infection cycle.