bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatitis C Virus Core Protein Suppresses NF-κB Activation and Cyclooxygenase-2 Expression by Direct Interaction with IκB Kinase β
Authors: Joo Myungsoo , Hahn Young S. , Kwon Minjae , Sadikot Ruxana T. , Blackwell Timothy S. , Christman John W. 
Published: May 2005

ABSTRACTIn addition to hepatocytes, hepatitis C virus (HCV) infects immune cells, including macrophages. However, little is known concerning the impact of HCV infection on cellular functions of these immune effector cells. Lipopolysaccharide (LPS) activates IκB kinase (IKK) signalsome and NF-κB, which leads to the expression of cyclooxygenase-2 (COX-2), which catalyzes production of prostaglandins, potent effectors on inflammation and possibly hepatitis. Here, we examined whether expression of HCV core interferes with IKK signalsome activity and COX-2 expression in activated macrophages. In reporter assays, HCV core inhibited NF-κB activation in RAW 264.7 and MH-S murine macrophage cell lines treated with bacterial LPS. HCV core inhibited IKK signalsome and IKKβ kinase activities induced by tumor necrosis factor alpha in HeLa cells and coexpressed IKKγ in 293 cells, respectively. HCV core was coprecipitated with IΚΚβ and prevented nuclear translocation of IKKβ. NF-κB activation by either LPS or overexpression of IKKβ was sufficient to induce robust expression of COX-2, which was markedly suppressed by ectopic expression of HCV core. Together, these data indicate that HCV core suppresses IKK signalsome activity, which blunts COX-2 expression in macrophages. Additional studies are necessary to determine whether interrupted COX-2 expression by HCV core contributes to HCV pathogenesis.
Role of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand in Immune Response to Influenza Virus Infection in Mice
Authors: Ishikawa Eri , Nakazawa Masatoshi , Yoshinari Masahiro , Minami Mutsuhiko 
Published: May 2005

ABSTRACTTumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis of various tumor cells but not normal cells. However, various cytokines and virus infection differentially regulate TRAIL and TRAIL receptor expression. It has been demonstrated that virus infection changes the pattern of human TRAIL-receptor expression on normal cells, which were resistant to TRAIL-mediated apoptosis, and makes them susceptible to TRAIL-mediated apoptosis. Since previous studies on the function of TRAIL have been performed mainly in vitro, its physiological role in the immune response to virus infection remains unknown. In the present study, we investigated the expression of TRAIL in the lungs of influenza virus-infected mice and the function of TRAIL in the immune response to infection. Influenza virus infection increased TRAIL mRNA expression in the lung. TRAIL protein expression was induced on NK cells in the lung 4 days after infection. At 7 days after infection, TRAIL protein expression was also detected on CD4+and CD8+T cells. However, NK cells and T cells in the lungs of uninfected mice did not express a detectable level of TRAIL on their cell surfaces. DR5, which is a mouse TRAIL receptor, was also induced to express after virus infection. Expression of both TRAIL and DR5 mRNAs was reduced to normal level at 6 weeks after virus infection. Administration of anti-TRAIL monoclonal antibody, which blocks TRAIL without killing TRAIL-expressing cells, to mice during influenza virus infection significantly delayed virus clearance in the lung. These results suggest that TRAIL plays an important role in the immune response to virus infection.
Single Amino Acid Insertions at the Junction of the Sindbis Virus E2 Transmembrane Domain and Endodomain Disrupt Virus Envelopment and Alter Infectivity
Authors: Hernandez Raquel , Ferreira Davis , Sinodis Christine , Litton Katherine , Brown Dennis T. 
Published: May 2005

ABSTRACT
The final steps in the envelopment of Sindbis virus involve specific interactions of the E2 endodomain with the virus nucleocapsid. Deleting E2 K at position 391 (E2 ΔK391) resulted in the disruption of virus assembly in mammalian cells but not insect cells (host range mutant). This suggested unique interactions of the E2 ΔK391 endodomain with the different biochemical environments of the mammalian and insect cell lipid bilayers. To further investigate the role of the amino acid residues located at or around position E2 391 and constraints on the length of the endodomain on virus assembly, amino acid insertions/substitutions at the transmembrane/endodomain junction were constructed. An additional K was inserted at amino acid position 392 (KK391/392), a K→F substitution at position 391 was constructed (F391), and an additional F was inserted at 392 (FF391/392). These changes should lengthen the endodomain in the KK391/392 insertion mutant or shorten the endodomain in the FF391/392 mutant. The mutant FF391/392 grown in BHK cells formed virus particles containing extruded material not found on wild-type virus. This characteristic was not seen in FF391/392 virus grown in insect cells. The mutant KK391/392 grown in BHK cells was defective in the final membrane fission reaction, producing multicored or conjoined virus particles. The production of these aberrant particles was ameliorated when the KK391/392 mutant was grown in insect cells. These data indicate that there is a critical minimal spanning distance from the E2 membrane proximal amino acid at position 391 and the conserved E2 Y400 residue. The observed phenotypes of these mutants also invoke an important role of the specific host membrane lipid composition on virus architecture and infectivity.
Cytokine Responses in Severe Acute Respiratory Syndrome Coronavirus-Infected Macrophages In Vitro: Possible Relevance to Pathogenesis
Authors: Cheung Chung Y. , Poon Leo L. M. , Ng Iris H. Y. , Luk Winsie , Sia Sin-Fun , Wu Mavis H. S. , Chan Kwok-Hung , Yuen Kwok-Yung , Gordon Siamon , Guan Yi , Peiris Joseph S. M. 
Published: May 2005

ABSTRACTThe pathogenesis of severe acute respiratory syndrome (SARS) remains unclear. Macrophages are key sentinel cells in the respiratory system, and it is therefore relevant to compare the responses of human macrophages to infections with the SARS coronavirus (SARS-CoV) and other respiratory viruses. Primary human monocyte-derived macrophages were infected with SARS-CoV in vitro. Virus replication was monitored by measuring the levels of positive- and negative-strand RNA, by immunofluorescence detection of the SARS-CoV nucleoprotein, and by titration of the infectious virus. The gene expression profiles of macrophages infected with SARS-CoV, human coronavirus 229E, and influenza A (H1N1) virus were compared by using microarrays and real-time quantitative reverse transcriptase PCR. Secreted cytokines were measured with an enzyme-linked immunosorbent assay. SARS-CoV initiated viral gene transcription and protein synthesis in macrophages, but replication was abortive and no infectious virus was produced. In contrast to the case with human coronavirus 229E and influenza A virus, there was little or no induction of beta interferon (IFN-β) in SARS-CoV-infected macrophages. Furthermore, SARS-CoV induced the expression of chemokines such as CXCL10/IFN-γ-inducible protein 10 and CCL2/monocyte chemotactic protein 1. The poor induction of IFN-β, a key component of innate immunity, and the ability of the virus to induce chemokines could explain aspects of the pathogenesis of SARS.
Characterization of Human Cytomegalovirus Glycoprotein-Induced Cell-Cell Fusion
Authors: Kinzler Eric R. , Compton Teresa 
Published: May 2005

ABSTRACT
Human cytomegalovirus (CMV) infection is dependent on the functions of structural glycoproteins at multiple stages of the viral life cycle. These proteins mediate the initial attachment and fusion events that occur between the viral envelope and a host cell membrane, as well as virion-independent cell-cell spread of the infection. Here we have utilized a cell-based fusion assay to identify the fusogenic glycoproteins of CMV. To deliver the glycoprotein genes to various cell lines, we constructed recombinant retroviruses encoding gB, gH, gL, and gO. Cells expressing individual CMV glycoproteins did not form multinucleated syncytia. Conversely, cells expressing gH/gL showed pronounced syncytium formation, although expression of gH or gL alone had no effect. Anti-gH neutralizing antibodies prevented syncytium formation. Coexpression of gB and/or gO with gH/gL did not yield detectably increased numbers of syncytia. For verification, these results were recapitulated in several cell lines. Additionally, we found that fusion was cell line dependent, as nonimmortalized fibroblast strains did not fuse under any conditions. Thus, the CMV gH/gL complex has inherent fusogenic activity that can be measured in certain cell lines; however, fusion in fibroblast strains may involve a more complex mechanism involving additional viral and/or cellular factors.
Regulatory T Cells Suppress In Vitro Proliferation of Virus-Specific CD8+T Cells during Persistent Hepatitis C Virus Infection
Authors: Rushbrook Simon M. , Ward Scott M. , Unitt Esther , Vowler Sarah L. , Lucas Michaela , Klenerman Paul , Alexander Graeme J. M. 
Published: May 2005

ABSTRACTThe basis of chronic infection following exposure to hepatitis C virus (HCV) infection is unexplained. One factor may be the low frequency and immature phenotype of virus-specific CD8+T cells. The role of CD4+CD25+T regulatory (Treg) cells in priming and expanding virus-specific CD8+T cells was investigated. Twenty HLA-A2-positive patients with persistent HCV infection and 46 healthy controls were studied. Virus-specific CD8+T-cell proliferation and gamma interferon (IFN-γ) frequency were analyzed with/without depletion of Tregcells, using peptides derived from HCV, Epstein-Barr virus (EBV), and cytomegalovirus (CMV). CD4+CD25+Tregcells inhibited anti-CD3/CD28 CD8+T-cell proliferation and perforin expression. Depletion of CD4+CD25+Tregcells from chronic HCV patients in vitro increased HCV and EBV peptide-driven expansion (P= 0.0005 andP= 0.002, respectively) and also the number of HCV- and EBV-specific IFN-γ-expressing CD8+T cells. Although stimulated CD8+T cells expressed receptors for transforming growth factor beta and interleukin-10, the presence of antibody to transforming growth factor beta and interleukin-10 had no effect on the suppressive effect of CD4+CD25+regulatory T cells on CD8+T-cell proliferation. In conclusion, marked CD4+CD25+regulatory T-cell activity is present in patients with chronic HCV infection, which may contribute to weak HCV-specific CD8+T-cell responses and viral persistence.
Disruption of Human TRIM5α Antiviral Activity by Nonhuman Primate Orthologues
Authors: Berthoux Lionel , Sebastian Sarah , Sayah David M. , Luban Jeremy 
Published: May 2005

ABSTRACT

TRIM5 is a determinant of species-specific differences in susceptibility to infection by retroviruses bearing particular capsids. Human immunodeficiency virus type 1 (HIV-1) infection is blocked by the alpha isoform of macaque TRIM5 (TRIM5α
rh
) or by the product of the owl monkey TRIM5-cyclophilin A gene fusion (TRIMCyp). Human TRIM5α potently restricts specific strains of murine leukemia virus (N-MLV) but has only a modest effect on HIV-1. The amino termini of TRIM5 orthologues are highly conserved and possess a coiled-coil domain that promotes homomultimerization. Here we show that heterologous expression of TRIM5α
rh
or TRIMCyp in human cells interferes with the anti-N-MLV activity of endogenous human TRIM5α (TRIM5α
hu
). Deletion of the cyclophilin domain from TRIMCyp has no effect on heteromultimerization or colocalization with TRIM5α
hu
but prevents interference with anti-N-MLV activity. These data demonstrate that TRIM5 orthologues form heteromultimers and indicate that C-terminal extensions alter virus recognition by multimers of these proteins.
Investigation of the Multimerization Region of the Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Protein K-bZIP: the Proposed Leucine Zipper Region Encodes a Multimerization Domain with an Unusual Structure
Authors: Al Mehairi Salama , Cerasoli Eleanora , Sinclair Alison J. 
Published: May 2005

ABSTRACT

The
K8
gene of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) shares many functional similarities with the
BZLF1
gene of Epstein-Barr virus. The protein products of
K8
and
BZLF1
, K-bZIP (RAP, K8) and Zta (BZLF1, ZEBRA, Z) have both been proposed to be members of the bZIP family of transcription factors, forming multimers via a coiled-coil motif termed a leucine zipper. Substantial evidence supporting this model for Zta is published. Here, we demonstrate that the proposed leucine zipper region of K-bZIP (amino acids 182 to 218) is required for multimer formation but that it does not fold as a coiled coil.
Determination of the Minimal Distance between the Matrix and Transmembrane Domains of the Large Hepatitis B Virus Envelope Protein
Authors: Kluge Britta , Schläger Michaela , Pairan Alexander , Bruss Volker 
Published: May 2005

ABSTRACT
The cytosolic matrix domain (MD) located between amino acids (aa) 103 and 124 of the large hepatitis B virus envelope protein L is essential for virion formation. We reduced the distance between MD and the transmembrane domain (TD; aa 254 to 272) by deletions starting at aa 132. Six mutants with deletions of up to aa 234 were wild type, and four mutants with slightly larger deletions were blocked with respect to virion morphogenesis. Thus, the minimal distance between MD and TD was around 26 aa. This spacer might be required by MD to reach contact sites on the capsid.
The Morphology and Composition of Influenza A Virus Particles Are Not Affected by Low Levels of M1 and M2 Proteins in Infected Cells
Authors: Bourmakina Svetlana V. , García-Sastre Adolfo 
Published: May 2005

ABSTRACT
We generated a recombinant influenza A virus (Mmut) that produced low levels of matrix (M1) and M2 proteins in infected cells. Mmut virus propagated to significantly lower titers than did wild-type virus in cells infected at low multiplicity. By contrast, virion morphology and incorporation of viral proteins and vRNAs into virus particles were similar to those of wild-type virus. We propose that a threshold amount of M1 protein is needed for the assembly of viral components into an infectious particle and that budding is delayed in Mmut virus-infected cells until sufficient levels of M1 protein accumulate at the plasma membrane.
Enhanced Immunogenicity of gp120 Protein When Combined with Recombinant DNA Priming To Generate Antibodies That Neutralize the JR-FL Primary Isolate of Human Immunodeficiency Virus Type 1
Authors: Wang Shixia , Arthos James , Lawrence John M. , Van Ryk Donald , Mboudjeka Innocent , Shen Siyuan , Chou Te-hui W. , Montefiori David C. , Lu Shan 
Published: May 2005

ABSTRACT
Strategies are needed for human immunodeficiency virus type 1 vaccine development that improves the neutralizing antibody response against primary isolates of the virus. Here we examined recombinant DNA priming followed by subunit protein boosting as a strategy to generate neutralizing antibodies. Both plasmid-based and recombinant protein envelope (Env) glycoprotein immunogens were derived from a primary viral isolate, JR-FL. Serum from rabbits immunized with either gp120 or gp140 DNA vaccines delivered by gene gun inoculation followed by recombinant gp120 protein boosting was capable of neutralizing JR-FL. Neither the DNA vaccines alone nor the gp120 protein alone generated a detectable neutralizing antibody response against this virus. Neutralizing antibody responses using gp120 DNA and gp140 DNA for priming were similar. The results suggest that Env DNA priming followed by gp120 protein boosting provides an advantage over either approach alone for generating a detectable neutralizing antibody response against primary isolates that are not easily neutralized.
Reversible Acid-Induced Inactivation of the Membrane Fusion Protein of Semliki Forest Virus
Authors: Waarts Barry-Lee , Smit Jolanda M. , Aneke Onwuchekwa J. C. , McInerney Gerald M. , Liljeström Peter , Bittman Robert , Wilschut Jan 
Published: May 2005

ABSTRACT
Previously, it has been shown that the exposure of Semliki Forest virus (SFV) to a mildly acidic environment induces a rapid and complete loss of the ability of the virus to bind and fuse to target membranes added subsequently. In the present study, incubation of SFV at low pH followed by a specific reneutralization step resulted in a partial reversion of this loss of viral fusion capacity, as assessed in a liposomal model system. Also, the ability of the viral E1 fusion protein to undergo liposome-stimulated trimerization was restored. Furthermore, acid-treated and neutralized SFV largely retained infectivity. Exposure of SFV to low pH induced dissociation of the E1/E2 heterodimer, which was not reversed upon neutralization. It is concluded that the SFV E1 fusion protein, after acid-induced dissociation from E2, rapidly adopts an intermediate, nontrimeric conformation in which it is no longer able to interact with target membrane lipids. Neutralization restores the ability of E1 to interact with membranes. This interaction, however, remains strictly dependent on low pH.
Outcomes of Border Health Spanish/English Chronic Disease Self-management Programs
Authors: Lorig Kate R. , Ritter Philip L. , Jacquez Anna 
Published: May 2005

Purpose The purpose of this study was to evaluate the community-based Chronic Disease Self-management Program (CDSMP) and the Spanish-language version (Tomando Control de Su Salud) programs as delivered in settings along the Texas/New Mexico/Mexico border. The programs had proven effective in randomized trials, and the authors wished to determine if they would be as effective when administered by others to different populations. Methods The El Paso Diabetes Association administered the CDSMP and Tomando to 445 persons with chronic illness (two thirds with diabetes) in Texas, New Mexico, and Mexico. Four-month and 1-year outcomes were compared to baseline using t tests of change scores. Regression models were used to test whether baseline demographics and self-efficacy were associated with positive outcomes of the programs. Results Participants showed improvements in health behaviors, health status, and self-efficacy at both 4 month and 1 year. Baseline self-efficacy and 4-month change in self-efficacy were significantly associated with improved 1- year outcomes. Conclusions The CDSMP and Tomando are effective when used in settings other than that of the original study for populations other than those for which they were initially developed.
Diabetes Management in San Diego’s Chamorro Community
Authors: Wu Phillis L. , Sadler Georgia Robins , Nguyen Victoria , Shi Manli , Gilpin Elizabeth A. , Cruz Lee Ann C. , Blas Lillian A. , Cruz Jesus A. 
Published: May 2005

Purpose The purpose of this study was to assess the diabetes risk status, incidence, and morbidity within San Diego’s Chamorro community as a foundation to help community leaders and health care providers create culturally customized health promotion interventions. Methods The Behavioral Risk Factor Surveillance Survey was used to query a randomly selected, convenience sample of San Diego Chamorros (N = 228) drawn from the Chamorro Directory International. Based on individual survey responses, participants were mailed personalized health-promoting information. Subsequently, they received information that addressed the most commonly observed overall threats to the Chamorro community’s health. Results A higher than average prevalence of diabetes and gestational diabetes was reported by study participants along with a high prevalence of the risk factors associated with the premature onset of diabetes and its consequences. Conclusion Collaborative partnerships between health professionals and community leaders can help identify opportunities and strategies for improving the health of the nation’s population subgroups. San Diego’s Chamorro community leaders now have a clearer understanding of the prevalence of diabetes risk factors within their community and can begin working with public health educators to create culturally aligned diabetes prevention and management programs. Given the willingness of Chamorro leaders to get involved in the development of a diabetes awareness campaign and the community’s closely knit social network, it should be possible to promote (1) community participation in the intervention program, (2) an increase in the community’s adherence to recommended behavioral changes, and (3) identification of additional program modifications that will further enhance the program’s cultural relevance.
Population-Based Assessment of Diabetes Care and Self-management Among Puerto Rican Adults in New York City
Authors: Hosler Akiko S. , Melnik Thomas A. 
Published: May 2005

Purpose The purpose of this study was to assess the status of diabetes medical care and self-management among adult Puerto Ricans in New York City. Methods A random-digit-dialing telephone survey with a dual-frame sampling design was employed to obtain a probability sample of adult Puerto Ricans with diagnosed diabetes (n = 606). Demographic characteristics, health status, and indicators of diabetes medical care and self- management were collected using the standard Behavioral Risk Factor Surveillance System (BRFSS) questionnaire. A statewide sample of adults with diagnosed diabetes (n = 232) was obtained from the BRFSS for comparison. Results Compared to New York State adults, Puerto Ricans were significantly less likely to receive annual A1C testing (72.7% vs 84.9%), cholesterol testing (67.5% vs 87.2%), blood-pressure-lowering medication (82.4% vs 91.9%), and pneumococcal vaccination (19.3% vs 28.5%, among those aged 18 to 64 years). Puerto Ricans were also less likely to take aspirin every day or every other day to prevent cardiovascular complications (30.6% vs 40.7%). Puerto Ricans were younger and more likely to have lower educational attainment and lower income than New York State adults, but they were not significantly disadvantaged in access to health care indicated by rates of health insurance coverage, having a particular place for medical care, and frequencies of seeing a provider for diabetes. Conclusions These findings support the need to introduce culturally sensitive and linguistically appropriate diabetes education programs for Puerto Ricans and continue system-based diabetes care quality improvement efforts in the areas of prevention and control of cardiovascular complications, adult immunization, and A1C testing.