bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ahi-1
, a Novel Gene Encoding a Modular Protein with WD40-Repeat and SH3 Domains, Is Targeted by the
Ahi-1
and
Mis-2
Provirus Integrations
Authors: Jiang Xiaoyan , Hanna Zaher , Kaouass Mohammadi , Girard Luc , Jolicoeur Paul 
Published: October 2002

ABSTRACT

The
Ahi-1
locus was initially identified as a common helper provirus integration site in Abelson pre-B-cell lymphomas and shown to be closely linked to the c-
myb
proto-oncogene. Since no significant alteration of c-
myb
expression was found in Abelson murine leukemia virus-induced pre-B-lymphomas harboring a provirus inserted within the
Ahi-1
locus, this suggested that it harbors another gene whose dysregulation is involved in tumor formation. Here we report the identification of a novel gene (
Ahi-1
) targeted by these provirus insertional mutations and the cloning of its cDNA. The Ahi-1 proviral insertions were found at the 3′ end of the gene, in an inverse transcriptional orientation, with most of them located around and downstream of the last exon, whereas another insertion was within intron 22. In addition, another previously identified provirus insertion site, Mis-2, was found to map within the 16th intron of the
Ahi-1
gene. The
Ahi-1
cDNA encodes a 1,047-amino-acid protein. The predicted Ahi-1 protein is a modular protein that contains one SH3 motif and seven WD40 repeats. The
Ahi-1
gene is conserved in mammals and encodes two major RNA species of 5 and 4.2 kb and several other shorter splicing variants. The
Ahi-1
gene is expressed in mouse embryos and in several organs of the mouse and rat, notably at high levels in the brain and testes. In tumor cells harboring insertional mutations in
Ahi-1
, truncated
Ahi-1
/viral fused transcripts were identified, including some splicing variants with deletion of the SH3 domain. Therefore,
Ahi-1
is a novel gene targeted by provirus insertion and encoding a protein that exhibits several features of a signaling molecule. Thus,
Ahi-1
may play an important role in signal transduction in normal cells and may be involved in tumor development, possibly in cooperation with other oncogenes (such as v-
abl
and c-
myc
) or with a tumor suppressor gene (
Nf1
), since Ahi-1 insertion sites were identified in tumors harboring v-
abl
defective retroviruses or a c-
myc
transgene or in tumors exhibiting deletion of
Nf1
.
Overexpression of Interleukin-2 by a Recombinant Herpes Simplex Virus Type 1 Attenuates Pathogenicity and Enhances Antiviral Immunity
Authors: Ghiasi Homayon , Osorio Yanira , Perng Guey-Chuen , Nesburn Anthony B. , Wechsler Steven L. 
Published: October 2002

ABSTRACTThe expression of interleukin-2 (IL-2) has been implicated in the modulation of the outcome of ocular infection with herpes simplex virus type 1 (HSV-1); however, its effects remain controversial. To clarify the role of IL-2, we constructed a recombinant HSV-1 (HSV-IL-2) that expresses two copies of the murine IL-2 gene under the control of the latency-associated transcript (LAT) promoter of HSV-1 in a LAT-negative virus. In tissue culture, the replication of the HSV-IL-2 was 100-fold lower than that of the wild-type virus at a low multiplicity of infection (MOI). Addition of recombinant anti-IL-2 polyclonal antibody markedly enhanced HSV-IL-2 replication in tissue culture. In the 7-day period after ocular infection of BALB/c mice, the replication of HSV-IL-2 was significantly lower than that of wild-type virus in tear cultures, whole eyes, and brain, but was equivalent to wild-type replication in the trigeminal ganglia. Ocular challenge of BALB/c mice with HSV-IL-2 alone, at an MOI that resulted in only 13% survival when parental virus was used, was associated with 90% survival. This decrease in virulence was further shown to be attributable to the expression of IL-2 by coinfection of mice with HSV-IL-2 and the parental virus. This resulted in a decrease in virulence of the parental virus (5% survival when administered alone versus 50% survival on coinfection with HSV-IL-2). The survival of HSV-IL-2-infected mice was compromised by depletion of either IL-2, CD4+, or CD8+T cells (50% survival) and abolished completely by depletion of both T-cell subtypes. Moreover, depletion of CD4+T cells, CD8+T cells, or both increased the titers of HSV-IL-2 in the tears, eyes, trigeminal ganglia, and brains of infected mice, so that titers were equivalent to or higher than that of the parental virus. These results suggest that IL-2 expression by recombinant HSV-1 reduces virulence and that depletion of IL-2 or T cells increases virulence in HSV-1-infected mice.
Homomultimerization of the Coxsackievirus 2B Protein in Living Cells Visualized by Fluorescence Resonance Energy Transfer Microscopy
Authors: van Kuppeveld Frank J. M. , Melchers Willem J. G. , Willems Peter H. G. M. , Gadella, Theodorus W. J. 
Published: October 2002

ABSTRACT
The 2B protein of enteroviruses is the viral membrane-active protein that is responsible for the modifications in host cell membrane permeability that take place in enterovirus-infected cells. The 2B protein shows structural similarities to the group of lytic polypeptides, polypeptides that permeate membranes either by forming multimeric membrane-integral pores or, alternatively, by lying parallel to the lipid bilayer and disturbing the curvature and symmetry of the membrane. Our aim is to gain more insight into the molecular architecture of the 2B protein in vivo. In this study, the possible existence of multimers of the coxsackie B3 virus 2B protein in single living cells was explored by fluorescence resonance energy transfer (FRET) microscopy. FRET between fusion proteins 2B-ECFP and 2B-EYFP (enhanced cyan and yellow fluorescent variants of green fluorescent protein) was monitored by using spectral imaging microscopy (SPIM) and fluorescence lifetime imaging microscopy (FLIM). Both techniques revealed the occurrence of intermolecular FRET between 2B-ECFP and 2B-EYFP, providing evidence for the formation of protein 2B homomultimers. Putative models for the mode of action of the membrane-active 2B protein and the formation of membrane-integral pores by 2B multimers are discussed.
Nuclear Localization of Human Immunodeficiency Virus Type 1 Preintegration Complexes (PICs): V165A and R166A Are Pleiotropic Integrase Mutants Primarily Defective for Integration, Not PIC Nuclear Import
Authors: Limón Ana , Devroe Eric , Lu Richard , Ghory Hina Z. , Silver Pamela A. , Engelman Alan 
Published: October 2002

ABSTRACTRetroviral replication requires the integration of reverse-transcribed viral cDNA into a cell chromosome. A key barrier to forming the integrated provirus is the nuclear envelope, and numerous regions in human immunodeficiency virus type 1 (HIV-1) have been shown to aid the nuclear localization of viral preintegration complexes (PICs) in infected cells. One region in integrase (IN), composed of Val-165 and Arg-166, was reportedly essential for HIV-1 replication and nuclear localization in all cell types. In this study we confirmed that HIV-1V165Aand HIV-1R166Awere replication defective and that less mutant viral cDNA localized to infected cell nuclei. However, we present three lines of evidence that argue against a specific role for Val-165 and Arg-166 in PIC nuclear import. First, results of transient transfections revealed that V165A FLAG-tagged IN and green fluorescent protein-IN fusions carrying either V165A or R166A predominantly localized to cell nuclei. Second, two different strains of previously described class II IN mutant viruses displayed similar nuclear entry profiles to those observed for HIV-1V165Aand HIV-1R166A, suggesting that defective nuclear import may be a common phenotype of replication-defective IN mutant viruses. Third, V165A and R166A mutants were defective for in vitro integration activity, when assayed both as PICs isolated from infected T-cells and as recombinant IN proteins purified fromEscherichia coli.Based on these results, we conclude that HIV-1V165Aand HIV-1R166Aare pleiotropic mutants primarily defective for IN catalysis and that Val-165 and Arg-166 do not play a specific role in the nuclear localization of HIV-1 PICs in infected cells.
Prevalence and Quantitation of Species C Adenovirus DNA in Human Mucosal Lymphocytes
Authors: Garnett C. T. , Erdman D. , Xu W. , Gooding Linda R. 
Published: October 2002

ABSTRACTThe common species C adenoviruses (serotypes Ad1, Ad2, Ad5, and Ad6) infect more than 80% of the human population early in life. Following primary infection, the virus can establish an asymptomatic persistent infection in which infectious virions are shed in feces for several years. The probable source of persistent virus is mucosa-associated lymphoid tissue, although the molecular details of persistence or latency of adenovirus are currently unknown. In this study, a sensitive real-time PCR assay was developed to quantitate species C adenovirus DNA in human tissues removed for routine tonsillectomy or adenoidectomy. Using this assay, species C DNA was detected in Ficoll-purified lymphocytes from 33 of 42 tissue specimens tested (79%). The levels varied from fewer than 10 to greater than 2 × 106copies of the adenovirus genome/107cells, depending on the donor. DNA from serotypes Ad1, Ad2, and Ad5 was detected, while the rarer serotype Ad6 was not. When analyzed as a function of donor age, the highest levels of adenovirus genomes were found among the youngest donors. Antibody-coated magnetic beads were used to purify lymphocytes into subpopulations and determine whether viral DNA could be enriched within any purified subpopulations. Separation of T cells (CD4/8- expressing and/or CD3-expressing cells) enriched viral DNA in each of nine donors tested. In contrast, B-cell purification (CD19-expressing cells) invariably depleted or eliminated viral DNA. Despite the frequent finding of significant quantities of adenovirus DNA in tonsil and adenoid tissues, infectious virus was rarely present, as measured by coculture with permissive cells. These findings suggest that human mucosal T lymphocytes may harbor species C adenoviruses in a quiescent, perhaps latent form.
Vγ4+T Cells Promote Autoimmune CD8+Cytolytic T-Lymphocyte Activation in Coxsackievirus B3-Induced Myocarditis in Mice: Role for CD4+Th1 Cells
Authors: Huber S. A. , Sartini D. , Exley M. 
Published: October 2002

ABSTRACTT cells expressing the Vγ4 T-cell receptor (TCR) promote myocarditis in coxsackievirus B3 (CVB3)-infected BALB/c mice. CD1, a major histocompatibility complex (MHC) class I-like molecule, is required for activation of Vγ4+cells. Once activated, Vγ4+cells initiate myocarditis through gamma interferon (IFN-γ)-mediated induction of CD4+T helper type 1 (Th1) cells in the infected animal. These CD4+Th1 cells are required for activation of an autoimmune CD8+αβ TCR+effector, which is the predominant pathogenic agent in this model of CVB3-induced myocarditis. Activated Vγ4+cells can adoptively transfer myocarditis into BALB/c mice infected with a nonmyocarditic variant of CVB3 (H310A1) but cannot transfer myocarditis into either uninfected or CD1−/−recipients, demonstrating the need for both infection and CD1 expression for Vγ4+cell function. In contrast, CD8+αβ TCR+cells transfer myocarditis into either infected CD1−/−or uninfected recipients, showing that once activated, the CD8+αβ TCR+effectors function independently of both virus and CD1. Vγ4+cells given to mice lacking CD4+T cells minimally activate the CD8+αβ TCR+cells. These studies show that Vγ4+cells determine CVB3 pathogenicity by their ability to influence both the CD4+and CD8+adaptive immune response. Vγ4+cells enhance CD4+Th1 (IFN-γ+) cell activation through IFN-γ- and CD1-dependent mechanisms. CD4+Th1 cells promote activation of the autoimmune CD8+αβ TCR+effectors.
Biology of Ovine Adenovirus Infection of Nonpermissive Cells
Authors: Kümin Daniel , Hofmann Christian , Rudolph Michael , Both Gerald W. , Löser Peter 
Published: October 2002

ABSTRACT

Nonhuman adenoviruses, including those of the genus
Atadenovirus
, have the potential to serve as vectors for vaccine and gene therapy applications in humans, since they are resistant to preexisting immunity induced by human adenoviruses in the majority of the population. In this study, we elucidate the outcome of infection by ovine adenovirus type 7 isolate 287 (OAdV) of several nonovine cell types. We show here that OAdV infects a wide range of nonovine cells but is unable to complete its replication cycle in any of them. In nonovine, nonfibroblast cells, viral replication is blocked at an early stage before the onset of, or early in, DNA replication. Some fibroblasts, on the other hand, allow viral DNA replication but block virus production at a later stage during or after the translation of late viral proteins. Late viral proteins are expressed in cells where viral DNA replication takes place, albeit at a reduced level. Significantly, late proteins are not properly processed, and their cellular distribution differs from that observed in infected ovine cells. Thus, our results clearly show that OAdV infection of all nonovine cells tested is abortive even if significant viral DNA replication occurs. These findings have significant positive implications with respect to the safety of the vector system and its future use in humans.
Isolation of an Intertypic Poliovirus Capsid Recombinant from a Child with Vaccine-Associated Paralytic Poliomyelitis
Authors: Martín Javier , Samoilovich Elena , Dunn Glynis , Lackenby Angie , Feldman Esphir , Heath Alan , Svirchevskaya Ekaterina , Cooper Gill , Yermalovich Marina , Minor Philip D. 
Published: October 2002

ABSTRACT
The isolation of a capsid intertypic poliovirus recombinant from a child with vaccine-associated paralytic poliomyelitis is described. Virus 31043 had a Sabin-derived type 3-type 2-type 1 recombinant genome with a 5′-end crossover point within the capsid coding region. The result was a poliovirus chimera containing the entire coding sequence for antigenic site 3a derived from the Sabin type 2 strain. The recombinant virus showed altered antigenic properties but did not acquire type 2 antigenic characteristics. The significance of the presence in nature of such poliovirus chimeras and the consequences for the current efforts to detect potentially dangerous vaccine-derived poliovirus strains are discussed in the context of the global polio eradication initiative.
Varicella-Zoster Virus (VZV) ORF17 Protein Induces RNA Cleavage and Is Critical for Replication of VZV at 37
o
C but Not 33
o
C
Authors: Sato Hitoshi , Callanan Lawrence D. , Pesnicak Lesley , Krogmann Tammy , Cohen Jeffrey I. 
Published: October 2002

ABSTRACT
Varicella-zoster virus (VZV) open reading frame 17 (ORF17) is homologous to herpes simplex virus (HSV) UL41, which encodes the viral host shutoff protein (vhs). HSV vhs induces degradation of mRNA and rapid shutoff of host protein synthesis. An antibody to ORF17 protein detected a 46-kDa protein in VZV-infected cells. While HSV vhs is located in virions, VZV ORF17 protein was not detectable in virions. ORF17 protein induced RNA cleavage, but to a substantially lesser extent than HSV-1 vhs. Expression of ORF17 protein did not inhibit expression from a β-galactosidase reporter plasmid, while HSV type 1 vhs abolished reporter expression. Two VZV ORF17 deletion mutants were constructed to examine the role of ORF17 in virus replication. While the ORF17 VZV mutants grew to peak titers that were similar to those of the parental virus at 33°C, the ORF17 mutants grew to 20- to 35-fold-lower titers than parental virus at 37°C. ORF62 protein was distributed in a different pattern in the nuclei and cytoplasm of cells infected with an ORF17 deletion mutant at 37°C compared to 33°C. Inoculation of cotton rats with the ORF17 deletion mutant resulted in a level of latent infection similar to that produced by inoculation with the parental virus. The importance of ORF17 protein for viral replication at 37°C but not at 33°C suggests that this protein may facilitate the growth of virus in certain tissues in vivo.
Hepatitis C Virus Nonstructural 5A Protein and Interferon Resistance: a New Model for Testing the Reliability of Mutational Analyses
Authors: Sarrazin Christoph , Herrmann Eva , Bruch Katharina , Zeuzem Stefan 
Published: October 2002

ABSTRACT

Presumably due to the capability of the hepatitis C virus (HCV) to evade the antiviral effects of alpha interferon, treatment is ineffective in more than half of chronically genotype HCV type 1 (HCV-1)-infected patients. Previous approaches to correlate the number of amino acid mutations within regions of HCV nonstructural (NS)-5A protein with virologic treatment response provided conflicting results. In the present study, we developed a new mathematical model to investigate NS5A sequences of HCV-1-infected patients. The mean number of all mutations within the complete NS5A protein was significantly higher in virologic responders compared to nonresponders (
P
= 0.008 and
P
= 0.0001 for amino acid residues predicted on the surface of the NS5A protein). Differences did not achieve statistical significance for NS5A regions that are currently assumed to be functionally relevant (e.g., the interferon sensitivity-determining region, the RNA-activated protein kinase-binding domain, etc.). Analyses of smoothed mutational frequencies showed that the number of mutations in other NS5A regions correlated with virologic response. Such a correlation was observed for both genuine and randomly generated NS5A sequences. The existence of local accumulations of mutations within genuine NS5A isolates that truly correlated with treatment response was defined by a refined test procedure. Upon considering the predicted residue accessibility, we identified the main focus of mutations correlating with treatment response to be the sequence from amino acids 2350 to 2370. Thus, evaluation of NS5A mutations in correlation with treatment response is improved by consideration of functional and predicted conformational amino acid properties. As shown by simulations with randomly generated sequences, multiple analyses of simple counts of local NS5A amino acid mutations and correlation with treatment response are insufficient. For improvement of mutational analysis, a refined specific functional data test procedure is proposed.
Why men with prostate cancer want wider access to prostate specific antigen testing: qualitative study
Authors: Chapple Alison , Ziebland Sue , Shepperd Sasha , Miller Rachel , Herxheimer Andrew , McPherson Ann 
Published: October 2002

Abstract

Objectives:
To explore the attitudes of men with confirmed or suspected prostate cancer to testing for prostate specific antigen.

Design:
Qualitative interview study with a purposive sample.

Setting:
Great Britain.

Participants:
52 men with suspected or confirmed prostate cancer, recruited through general practitioners, urologists, patient support groups, and charities.

Results:
Almost all men remembered their prostate specific antigen test but recalled being given little information beforehand. Arguments in favour of increased access to testing included the belief that early diagnosis would reduce mortality, improve quality of life, and save the NHS money. Men also thought that a national screening programme should be available because symptoms can be ambiguous, screening for cancer is responsible health behaviour, and screening would encourage men to be tested. Four men who opposed a screening programme had gathered information alerting them to uncertainty about the benefits of treatment, and two regretted that they had been tested. Others thought that access to testing is restricted in the United Kingdom because of a lack of government backing, concerns about the accuracy of the test, and a lack of resources.

Conclusions:
The few men in this study who subscribed to the argument that evidence of the benefits of treatment is a prerequisite for a screening programme did not want to see screening introduced. Men who proposed an alternative set of principles for testing gave reasons that did not all relate to overoptimism about the benefits of early diagnosis. People who plan services and people who respond to requests for testing need to understand men's perspectives and concerns.
Natural experiment examining impact of aggressive screening and treatment on prostate cancer mortality in two fixed cohorts from Seattle area and Connecticut
Authors: Lu-Yao Grace , Albertsen Peter C , Stanford Janet L , Stukel Therese A , Walker-Corkery Elizabeth S , Barry Michael J 
Published: October 2002

AbstractObjective:To determine whether the more intensive screening and treatment for prostate cancer in the Seattle-Puget Sound area in 1987-90 led to lower mortality from prostate cancer than in Connecticut.Design:Natural experiment comparing two fixed cohorts from 1987 to 1997.Setting:Seattle-Puget Sound and Connecticut surveillance, epidemiology, and end results areas.Participants:Population based cohorts of male Medicare beneficiaries aged 65-79 drawn from the Seattle (n=94 900) and Connecticut (n=120 621) areas.Main outcome measures:Rates of screening for prostate cancer, treatment with radical prostatectomy and external beam radiotherapy, and prostate cancer specific mortality.Results:The prostate specific antigen testing rate in Seattle was 5.39 (95% confidence interval 4.76 to 6.11) times that of Connecticut, and the prostate biopsy rate was 2.20 (1.81 to 2.68) times that of Connecticut during 1987-90. The 10 year cumulative incidences of radical prostatectomy and external beam radiotherapy up to 1996 were 2.7% and 3.9% for Seattle cohort members compared with 0.5% and 3.1% for Connecticut cohort members. The adjusted rate ratio of prostate cancer mortality up to 1997 was 1.03 (0.95 to 1.11) in Seattle compared with Connecticut.Conclusion:More intensive screening for prostate cancer and treatment with radical prostatectomy and external beam radiotherapy among Medicare beneficiaries in the Seattle area than in the Connecticut area was not associated with lower prostate cancer specific mortality over 11 years of follow up.
Back, neck, and shoulder pain in Finnish adolescents: national cross sectional surveys
Authors: Hakala Paula , Rimpelä Arja , Salminen Jouko J , Virtanen Suvi M , Rimpelä Matti 
Published: October 2002

AbstractObjectives:To study changes in pain of the back and neck in adolescents between 1985 and 2001 and pain of the neck, shoulder, and lower back between 1991 and2001.Design:Biennial nationwide postal surveys, 1985-2001, and annual classroom surveys, 1996-2001.Setting:Finland.Participants:62 677 12, 14, 16, and 18 year olds and 127 217 14-16 year olds.Main outcome measures:Pain in the back and neck, neck and shoulder, or lower back, at least weekly.Results:Prevalence of pain in the back and neck was greater in the 1990s than in the 1980s and increased steadily from 1993 to 1997. Pain of the neck and shoulder and pain of the lower back was much more common in 1999 than in 1991 and in 2001 than in 1999. Pain was more common among girls and older groups: pain of the neck and shoulder affected 24% of girls and 12% of boys in 14 year olds, 38% of girls and 16% of boys in 16 year olds, and 45% of girls and 19% of boys in 18 year olds; pain in the lower back affected 8% of girls and 7% of boys in 14 year olds, 14% of girls and 11% of boys in 16 year olds, and 17% of boysand 13% of girls in 18 year olds.Conclusion:Pain in the neck, shoulder, and lower back is becoming morecommon in Finnish adolescents. This pain suggests a new disease burden of degenerativemusculoskeletal disorders in future adults.