bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Analysis of Influenza A/H3N2 and A/H1N1 Viruses Circulating in Vietnam from 2001 to 2006
Authors: Li Danjuan , Saito Reiko , Le Mai T. Q. , Nguyen Hang L. K. , Suzuki Yasushi , Shobugawa Yugo , Dinh Duc T. , Hoang Phuong V. M. , Tran Huong T. T. , Nghiem Ha K. , Hoang Long T. , Huynh Lien P. , Nguyen Hien T. , Nishikawa Makoto , Suzuki Hiroshi 
Published: October 2007

ABSTRACT
Influenza A virus has the ability to overcome immunity from previous infections through the acquisition of genetic changes. Thus, understanding the evolution of the viruses in humans is important for the surveillance and the selection of vaccine strains. A total of 30 influenza A/H3N2 viruses and 35 influenza A/H1N1 viruses that were collected in Vietnam from 2001 to 2006 were used to analyze the evolution of the hemagglutinin (HA), neuraminidase (NA), and matrix protein (M) genes. Phylogenetic analysis of individual gene segments revealed that the HA and the NA genes of the influenza A viruses evolved in a sequential way. However, the evolutionary pattern of the M gene proved to be nonlinear and was not linked with that of the HA and NA genes. Genetic drift in HA1 segments, especially in the antigenic sites of A/H3N2 viruses, occurred more frequently in A/H3N2 viruses than it did in A/H1N1 viruses. Two reassortants, one influenza A/H3N2 strain and one A/H1N1 strain, were found on the basis of the phylogenetic analysis of the three genes. While both genetic mutation and reassortment contributed to their evolution, the frequency of genetic changes and reassortment events differs between the two subtypes. As influenza viruses circulate throughout the year, we emphasize the importance of surveillance in tropical and subtropical zones, where the emergence of new strains may be detected earlier than it is in temperate zones.
Microevolution of
Helicobacter pylori
Type IV Secretion Systems in an Ulcer Disease Patient over a Ten-Year Period
Authors: Alvi Ayesha , Devi S. Manjulata , Ahmed Irshad , Hussain M. Abid , Rizwan Mohammed , Lamouliatte Hérve , Mégraud Francis , Ahmed Niyaz 
Published: October 2007

ABSTRACT

Helicobacter pylori cagA
and
vacA
genotypes have been used for almost a decade as stable entities to link the severity of gastritis and ulcer disease. We describe here microevolution of the two genomic islands,
cag
pathogenicity island (
cag
PAI; 40 kb) and
tfs3
(16 kb) from isolates obtained at inclusion (one subclone) and after a 10-year period (two subclones) from a duodenal ulcer patient. Our results indicate microevolution in
cagA
,
cagE
, and
cag7
genes of the
cag
PAI and open reading frames G, P, and L in
tfs3
, which possibly leads to inactivation or pseudogenization of these genes. Interestingly, no significant reduction in the severity of gastroduodenal pathology was found. These results point to an obvious difficulty in correlating the continuously evolving virulence factors such as the
cag
PAI genes with disease characteristics that appear to remain stable.
Comparison of Three Commercial Test Systems for Biotyping
Haemophilus influenzae
and
Haemophilus parainfluenzae
Authors: Munson Erik L. , Doern Gary V. 
Published: October 2007

ABSTRACT

The biotypes of
Haemophilus influenzae
and
Haemophilus parainfluenzae
isolates were determined with three commercially available biochemical test kits: the IDS RapID NH system, the
Neisseria-Haemophilus
identification test (NHI card), and the API NH strip. The API NH strip performed best, correctly classifying the biotypes of 371 of 380 (97.6%) different challenge strains.
Quantitation of HLA Proteins Incorporated by Human Immunodeficiency Virus Type 1 and Assessment of Neutralizing Activity of Anti-HLA Antibodies
Authors: Lakhashe Samir K. , Thakar Madhuri R. , Bharucha K. E. , Paranjape Ramesh S. 
Published: October 2007

ABSTRACT
Human anti-human leukocyte antigen (HLA) antibodies were assessed for neutralizing activity against human immunodeficiency virus type 1 (HIV-1) carrying HLA alleles with matching specificity. Multiparous women carrying anti-HLA antibodies were identified. Plasma samples from those women were confirmed as having antibodies that specifically bound to HLA proteins expressed on the peripheral blood mononuclear cells (PBMCs) of their husbands. A primary HIV-1 isolate was cultured in the husband's PBMCs so that the virus carried matching HLA alleles. To determine the HIV-1-neutralizing activity of anti-HLA antibodies, the infectivity of the virus for GHOST cells (which express green fluorescent protein after HIV infection) was investigated in the presence of a plasma sample positive for the respective anti-HLA antibody. A neutralization assay was also performed using purified immunoglobulin G (IgG) from two plasma samples, and two plasma samples were investigated in the presence of complement. The prerequisite for anti-HLA antibody-mediated neutralization is incorporation of HLA proteins by HIV-1. Therefore, the extent of incorporation of HLA proteins by the primary HIV-1 isolate was estimated. The ratios of HLA class I protein to HIV-1 capsid (p24) protein cultured in the PBMCs of two healthy individuals were 0.017 and 0.054. These ratios suggested that the HIV-1 strain used in the assay incorporated more HLA proteins than gp160 trimers. Anti-HLA antibody-positive plasma was found to contain antibodies that specifically reacted to HIV-1 carrying cognate HLA alleles. However, incubation of HIV-1 with anti-HLA antibody- positive plasma or purified IgG did not show a reduction in viral infectivity. HIV-1-neutralizing activity was also not detected in the presence of complement. This study shows that HIV-1 primary isolates cultured in PBMCs contain significant amounts of HLA proteins. However, the binding of antibodies to those HLA proteins does not mediate a reduction in viral infectivity.
Distinct RIG-I and MDA5 Signaling by RNA Viruses in Innate Immunity
Authors: Loo Yueh-Ming , Fornek Jamie , Crochet Nanette , Bajwa Gagan , Perwitasari Olivia , Martinez-Sobrido Luis , Akira Shizuo , Gill Michelle A. , García-Sastre Adolfo , Katze Michael G. , Gale Michael 
Published: October 2007

ABSTRACT

Alpha/beta interferon immune defenses are essential for resistance to viruses and can be triggered through the actions of the cytoplasmic helicases retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5). Signaling by each is initiated by the recognition of viral products such as RNA and occurs through downstream interaction with the IPS-1 adaptor protein. We directly compared the innate immune signaling requirements of representative viruses of the
Flaviviridae
,
Orthomyxoviridae
,
Paramyxoviridae
, and
Reoviridae
for RIG-I, MDA5, and interferon promoter-stimulating factor 1 (IPS-1). In cultured fibroblasts, IPS-1 was essential for innate immune signaling of downstream interferon regulatory factor 3 activation and interferon-stimulated gene expression, but the requirements for RIG-I and MDA5 were variable. Each was individually dispensable for signaling triggered by reovirus and dengue virus, whereas RIG-I was essential for signaling by influenza A virus, influenza B virus, and human respiratory syncytial virus. Functional genomics analyses identified cellular genes triggered during influenza A virus infection whose expression was strictly dependent on RIG-I and which are involved in processes of innate or adaptive immunity, apoptosis, cytokine signaling, and inflammation associated with the host response to contemporary and pandemic strains of influenza virus. These results define IPS-1-dependent signaling as an essential feature of host immunity to RNA virus infection. Our observations further demonstrate differential and redundant roles for RIG-I and MDA5 in pathogen recognition and innate immune signaling that may reflect unique and shared biologic properties of RNA viruses whose differential triggering and control of gene expression may impact pathogenesis and infection.
Comparison of Plasma Viremia and Antibody Responses in Macaques Inoculated with Envelope Variants of Single-Cycle Simian Immunodeficiency Virus Differing in Infectivity and Cellular Tropism
Authors: DeGottardi M. Quinn , Lew Sharon K. , Piatak Michael , Jia Bin , Feng Yang , Lee Sandra J. , Brenchley Jason M. , Douek Daniel C. , Kodama Toshiaki , Lifson Jeffrey D. , Evans David T. 
Published: October 2007

ABSTRACT

Molecular differences in the envelope glycoproteins of human immunodeficiency virus type 1 and simian immunodeficiency virus (SIV) determine virus infectivity and cellular tropism. To examine how these properties contribute to productive infection in vivo, rhesus macaques were inoculated with strains of single-cycle SIV (scSIV) engineered to express three different envelope glycoproteins with full-length (TM
open
) or truncated (TM
stop
) cytoplasmic tails. The 239 envelope uses CCR5 for infection of memory CD4
+
T cells, the 316 envelope also uses CCR5 but has enhanced infectivity for primary macrophages, and the 155T3 envelope uses CXCR4 for infection of both naive and memory CD4
+
T cells. Separate groups of six rhesus macaques were inoculated intravenously with mixtures of TM
open
and TM
stop
scSIV
mac
239, scSIV
mac
316, and scSIV
mac
155T3. A multiplex real-time PCR assay specific for unique sequence tags engineered into each virus was then used to measure viral loads for each strain independently. Viral loads in plasma peaked on day 4 for each strain and were resolved below the threshold of detection within 4 to 10 weeks. Truncation of the envelope cytoplasmic tail significantly increased the peak of viremia for all three envelope variants and the titer of SIV-specific antibody responses. Although peak viremias were similar for both R5- and X4-tropic viruses, clearance of scSIV
mac
155T3 TM
stop
was significantly delayed relative to the other strains, possibly reflecting the infection of a CXCR4
+
cell population that is less susceptible to the cytopathic effects of virus infection. These studies reveal differences in the peaks and durations of a single round of productive infection that reflect envelope-specific differences in infectivity, chemokine receptor specificity, and cellular tropism.
Novel Cytotoxic T-Lymphocyte Escape Mutation by a Three-Amino-Acid Insertion in the Human Immunodeficiency Virus Type 1 p6
Pol
and p6
Gag
Late Domain Associated with Drug Resistance
Authors: Cao Jianhong , McNevin John , McSweyn Matthew , Liu Yi , Mullins James I. , McElrath M. Juliana 
Published: October 2007

ABSTRACT

Cytolytic T lymphocytes (CTL) play a major role in controlling human immunodeficiency virus type 1 (HIV-1) infection. To evade immune pressure, HIV-1 is selected at targeted CTL epitopes, which may consequentially alter viral replication fitness. In our longitudinal investigations of the interplay between T-cell immunity and viral evolution following acute HIV-1 infection, we observed in a treatment-naïve patient the emergence of highly avid, gamma interferon-secreting, CD8
+
CTL recognizing an HLA-Cw*0102-restricted epitope, NSPTRREL (NL8). This epitope lies in the p6
Pol
protein, located in the transframe region of the Gag-Pol polyprotein. Over the course of infection, an unusual viral escape mutation arose within the p6
Pol
epitope through insertion of a 3-amino-acid repeat, NSPT(SPT)RREL, with a concomitant insertion in the p6
Gag
late domain, PTAPP(APP). Interestingly, this p6
Pol
insertion mutation is often selected in viruses with the emergence of antiretroviral drug resistance, while the p6
Gag
late-domain PTAPP motif binds Tsg101 to permit viral budding. These results are the first to demonstrate viral evasion of immune pressure by amino acid insertions. Moreover, this escape mutation represents a novel mechanism whereby HIV-1 can alter its sequence within both the Gag and Pol proteins with potential functional consequences for viral replication and budding.
Protective Immunity toPseudomonas aeruginosaInduced with a Capsid-Modified Adenovirus ExpressingP. aeruginosaOprF
Authors: Worgall Stefan , Krause Anja , Qiu JianPing , Joh Ju , Hackett Neil R. , Crystal Ronald G. 
Published: October 2007

ABSTRACTThis study focuses on the development of a new clinical vaccine candidate (AdOprF.RGD.Epi8) againstPseudomonas aeruginosausing an E1−E3−adenovirus (Ad) vector expressing OprF (AdOprF.RGD.Epi8) and modifications of the Ad genome providing two capsid changes: (i) modification of the Ad hexon gene to incorporate an immune-dominant OprF epitope (Epi8) into loop 1 of the hexon, enabling repeat administration to boost the anti-OprF immune response, and (ii) modification of the fiber gene to incorporate an integrin-binding RGD sequence to enhance gene delivery to antigen-presenting cells. Western analysis confirmed that AdOprF.RGD.Epi8 expresses OprF, contains Epi8 in the hexon protein, and enhances gene transfer to dendritic cells compared to AdOprF, a comparable Ad vector expressing OprF with an unmodified capsid. Intramuscular immunization of C57BL/6 mice with AdOprF.RGD.Epi8 resulted in the generation of anti-OprF antibodies at comparable levels to those induced following immunization with AdOprF, but immunization with AdOprF.RGD.Epi8 was associated with increased CD4 and CD8 gamma interferon T-cell responses against OprF as well as increased survival against lethal pulmonary challenge with agar-encapsulatedP. aeruginosa. Importantly, repeat administration of AdOprF.RGD.Epi8 resulted in boosting of the humoral anti-OprF response as well as increased protection, whereas no boosting could be achieved with repeat administration of AdOprF. This suggests that the capsid-modified AdOprF.RGD.Epi8 vector is a more effective immunogen compared to a comparable wild-type Ad capsid, making it a good candidate for an anti-P. aeruginosavaccine.
Mouse Cytomegalovirus MicroRNAs Dominate the Cellular Small RNA Profile during Lytic Infection and Show Features of Posttranscriptional Regulation
Authors: Dölken Lars , Perot Jonathan , Cognat Valérie , Alioua Abdelmalek , John Matthias , Soutschek Jürgen , Ruzsics Zsolt , Koszinowski Ulrich , Voinnet Olivier , Pfeffer Sébastien 
Published: October 2007

ABSTRACT
MicroRNAs (miRNAs) are small, noncoding RNA molecules that regulate gene expression at the posttranscriptional level. Originally identified in a variety of organisms ranging from plants to mammals, miRNAs have recently been identified in several viruses. Viral miRNAs may play a role in modulating both viral and host gene expression. Here, we report on the identification and characterization of 18 viral miRNAs from mouse fibroblasts lytically infected with the murine cytomegalovirus (MCMV). The MCMV miRNAs are expressed at early times of infection and are scattered in small clusters throughout the genome with up to four distinct miRNAs processed from a single transcript. No significant homologies to human CMV-encoded miRNAs were found. Remarkably, as soon as 24 h after infection, MCMV miRNAs constituted about 35% of the total miRNA pool, and at 72 h postinfection, this proportion was increased to more than 60%. However, despite the abundance of viral miRNAs during the early phase of infection, the expression of some MCMV miRNAs appeared to be regulated. Hence, for three miRNAs we observed polyuridylation of their 3′ end, coupled to subsequent degradation. Individual knockout mutants of two of the most abundant MCMV miRNAs, miR-m01-4 and miR-M44-1, or a double knockout mutant of miR-m21-1 and miR-M23-2, incurred no or only a very mild growth deficit in murine embryonic fibroblasts in vitro.
Structure of the
Acidianus
Filamentous Virus 3 and Comparative Genomics of Related Archaeal Lipothrixviruses
Authors: Vestergaard Gisle , Aramayo Ricardo , Basta Tamara , Häring Monika , Peng Xu , Brügger Kim , Chen Lanming , Rachel Reinhard , Boisset Nicolas , Garrett Roger A. , Prangishvili David 
Published: October 2007

ABSTRACT

Four novel filamentous viruses with double-stranded DNA genomes, namely,
Acidianus
filamentous virus 3 (AFV3), AFV6, AFV7, and AFV8, have been characterized from the hyperthermophilic archaeal genus
Acidianus
, and they are assigned to the
Betalipothrixvirus
genus of the family
Lipothrixviridae
. The structures of the approximately 2-μm-long virions are similar, and one of them, AFV3, was studied in detail. It consists of a cylindrical envelope containing globular subunits arranged in a helical formation that is unique for any known double-stranded DNA virus. The envelope is 3.1 nm thick and encases an inner core with two parallel rows of protein subunits arranged like a zipper. Each end of the virion is tapered and carries three short filaments. Two major structural proteins were identified as being common to all betalipothrixviruses. The viral genomes were sequenced and analyzed, and they reveal a high level of conservation in both gene content and gene order over large regions, with this similarity extending partly to the earlier described betalipothrixvirus
Sulfolobus islandicus
filamentous virus. A few predicted gene products of each virus, in addition to the structural proteins, could be assigned specific functions, including a putative helicase involved in Holliday junction branch migration, a nuclease, a protein phosphatase, transcriptional regulators, and glycosyltransferases. The AFV7 genome appears to have undergone intergenomic recombination with a large section of an AFV2-like viral genome, apparently resulting in phenotypic changes, as revealed by the presence of AFV2-like termini in the AFV7 virions. Shared features of the genomes include (i) large inverted terminal repeats exhibiting conserved, regularly spaced direct repeats; (ii) a highly conserved operon encoding the two major structural proteins; (iii) multiple overlapping open reading frames, which may be indicative of gene recoding; (iv) putative 12-bp genetic elements; and (v) partial gene sequences corresponding closely to spacer sequences of chromosomal repeat clusters.
Serum-Derived Hepatitis C Virus Infection of Primary Human Hepatocytes Is Tetraspanin CD81 Dependent
Authors: Molina Sonia , Castet Valerie , Pichard-Garcia Lydiane , Wychowski Czeslaw , Meurs Eliane , Pascussi Jean-Marc , Sureau Camille , Fabre Jean-Michel , SaCunha Antonio , Larrey Dominique , Dubuisson Jean , Coste Joliette , McKeating Jane , Maurel Patrick , Fournier-Wirth Chantal 
Published: October 2007

ABSTRACT
Hepatitis C virus-positive serum (HCVser, genotypes 1a to 3a) or HCV cell culture (JFH1/HCVcc) infection of primary normal human hepatocytes was assessed by measuring intracellular HCV RNA strands. Anti-CD81 antibodies and siRNA-CD81 silencing markedly inhibited (>90%) HCVser infection irrespective of HCV genotype, viral load, or liver donor, while hCD81-large intracellular loop (LEL) had no effect. However, JFH1/HCVcc infection of hepatocytes was modestly inhibited (40 to 60%) by both hCD81-LEL and anti-CD81 antibodies. In conclusion, CD81 is involved in HCVser infection of human hepatocytes, and comparative studies of HCVser versus JFH1/HCVcc infection of human hepatocytes and Huh-7.5 cells revealed that the cell-virion combination is determinant of the entry process.
Rational Design of a Multiepitope Vaccine Encoding T-Lymphocyte Epitopes for Treatment of Chronic Hepatitis B Virus Infections
Authors: Depla Erik , Van der Aa Annegret , Livingston Brian D. , Crimi Claire , Allosery Koen , De Brabandere Veronique , Krakover Jonathan , Murthy Sidharta , Huang Manley , Power Scott , Babé Lilia , Dahlberg Carol , McKinney Denise , Sette Alessandro , Southwood Scott , Philip Ramilla , Newman Mark J. , Meheus Lydie 
Published: October 2007

ABSTRACTProtein sequences from multiple hepatitis B virus (HBV) isolates were analyzed for the presence of amino acid motifs characteristic of cytotoxic T-lymphocyte (CTL) and helper T-lymphocyte (HTL) epitopes with the goal of identifying conserved epitopes suitable for use in a therapeutic vaccine. Specifically, sequences bearing HLA-A1, -A2, -A3, -A24, -B7, and -DR supertype binding motifs were identified, synthesized as peptides, and tested for binding to soluble HLA. The immunogenicity of peptides that bound with moderate to high affinity subsequently was assessed using HLA transgenic mice (CTL) and HLA cross-reacting H-2bxd(BALB/c × C57BL/6J) mice (HTL). Through this process, 30 CTL and 16 HTL epitopes were selected as a set that would be the most useful for vaccine design, based on epitope conservation among HBV sequences and HLA-based predicted population coverage in diverse ethnic groups. A plasmid DNA-based vaccine encoding the epitopes as a single gene product, with each epitope separated by spacer residues to enhance appropriate epitope processing, was designed. Immunogenicity testing in mice demonstrated the induction of multiple CTL and HTL responses. Furthermore, as a complementary approach, mass spectrometry allowed the identification of correctly processed and major histocompatibility complex-presented epitopes from human cells transfected with the DNA plasmid. A heterologous prime-boost immunization with the plasmid DNA and a recombinant MVA gave further enhancement of the immune responses. Thus, a multiepitope therapeutic vaccine candidate capable of stimulating those cellular immune responses thought to be essential for controlling and clearing HBV infection was successfully designed and evaluated in vitro and in HLA transgenic mice.
Lymphocytoid Choriomeningitis Virus Activates Plasmacytoid Dendritic Cells and Induces a Cytotoxic T-Cell Response via MyD88
Authors: Jung Andreas , Kato Hiroki , Kumagai Yutaro , Kumar Himanshu , Kawai Taro , Takeuchi Osamu , Akira Shizuo 
Published: October 2007

ABSTRACT

Toll-like receptors (TLRs) and retinoic acid-inducible gene I-like helicases (RLHs) are two major machineries recognizing RNA virus infection of innate immune cells. Intracellular signaling for TLRs and RLHs is mediated by their cytoplasmic adaptors, i.e., MyD88 or TRIF and IPS-1, respectively. In the present study, we investigated the contributions of TLRs and RLHs to the cytotoxic T-lymphocyte (CTL) response by using lymphocytoid choriomeningitis virus (LCMV) as a model virus. The generation of virus-specific cytotoxic T lymphocytes was critically dependent on MyD88 but not on IPS-1. Type I interferons (IFNs) are known to be important for the development of the CTL response to LCMV infection. Serum levels of type I IFNs and proinflammatory cytokines were mainly dependent on the presence of MyD88, although IPS-1
−/−
mice showed a decrease in IFN-α levels but not in IFN-β and proinflammatory cytokine levels. Analysis of
Ifna6
+/GFP
reporter mice revealed that plasmacytoid dendritic cells (DCs) are the major source of IFN-α in LCMV infection. MyD88
−/−
mice were highly susceptible to LCMV infection in vivo. These results suggest that recognition of LCMV by plasmacytoid DCs via TLRs is responsible for the production of type I IFNs in vivo. Furthermore, the activation of a MyD88-dependent innate mechanism induces a CTL response, which eventually leads to virus elimination.