bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of CD127 and KLRG1 Expression on Hepatitis C Virus-Specific CD8
+
T Cells Reveals the Existence of Different Memory T-Cell Subsets in the Peripheral Blood and Liver
Authors: Bengsch Bertram , Spangenberg Hans Christian , Kersting Nadine , Neumann-Haefelin Christoph , Panther Elisabeth , von Weizsäcker Fritz , Blum Hubert E. , Pircher Hanspeter , Thimme Robert 
Published: December 2006

ABSTRACT

The differentiation and functional status of virus-specific CD8
+
T cells is significantly influenced by specific and ongoing antigen recognition. Importantly, the expression profiles of the interleukin-7 receptor alpha chain (CD127) and the killer cell lectin-like receptor G1 (KLRG1) have been shown to be differentially influenced by repetitive T-cell receptor interactions. Indeed, antigen-specific CD8
+
T cells targeting persistent viruses (e.g., human immunodeficiency virus and Epstein-Barr virus) have been shown to have low CD127 and high KLRG1 expressions, while CD8
+
T cells targeting resolved viral antigens (e.g., FLU) typically display high CD127 and low KLRG1 expressions. Here, we analyzed the surface phenotype and function of hepatitis C virus (HCV)-specific CD8
+
T cells. Surprisingly, despite viral persistence, we found that a large fraction of peripheral HCV-specific CD8
+
T cells were CD127
+
and KLRG1
−
and had good proliferative capacities, thus resembling memory cells that usually develop following acute resolving infection. Intrahepatic virus-specific CD8
+
T cells displayed significantly reduced levels of CD127 expression but similar levels of KLRG1 expression compared to the peripheral blood. These results extend previous studies that demonstrated central memory (CCR7
+
) and early-differentiated phenotypes of HCV-specific CD8
+
T cells and suggest that insufficient stimulation of virus-specific CD8
+
T cells by viral antigen may be responsible for this alteration in HCV-specific CD8
+
T-cell differentiation during chronic HCV infection.
Sheep-Passaged Bovine Spongiform Encephalopathy Agent Exhibits Altered Pathobiological Properties in Bovine-PrP Transgenic Mice
Authors: Espinosa Juan Carlos , Andréoletti Olivier , Castilla Joaquín , Herva María Eugenia , Morales Mónica , Alamillo Elia , San-Segundo Fayna Díaz , Lacroux Caroline , Lugan Séverine , Salguero Francisco Javier , Langeveld Jan , Torres Juan María 
Published: December 2006

ABSTRACT

Sheep can be experimentally infected with bovine spongiform encephalopathy (BSE), and the ensuing disease is similar to scrapie in terms of pathogenesis and clinical signs. BSE infection in sheep is an animal and human health concern. In this study, the transmission in BoPrP-Tg110 mice of prions from BSE-infected sheep was examined and compared to the transmission of original cattle BSE in cattle and sheep scrapie prions. Our results indicate no transmission barrier for sheep BSE prions to infect BoPrP-Tg110 mice, but the course of the disease is accelerated compared to the effects of the original BSE isolate. The shortened incubation period of sheep BSE in the model was conserved in subsequent passage in BoPrP-Tg110 mice, indicating that it is not related to infectious titer differences. Biochemical signature, lesion profile, and PrP
Sc
deposition pattern of both cattle and sheep BSE were similar. In contrast, all three sheep scrapie isolates tested showed an evident transmission barrier and further adaptation in subsequent passage. Taken together, those data indicate that BSE agent can be altered by crossing a species barrier, raising concerns about the virulence of this new prion towards other species, including humans. The BoPrP-Tg110 mouse bioassay should be considered as a valuable tool for discriminating scrapie and BSE in sheep.
Viral Interactions in Human Lymphoid Tissue: Human Herpesvirus 7 Suppresses the Replication of CCR5-Tropic Human Immunodeficiency Virus Type 1 via CD4 Modulation
Authors: Lisco Andrea , Grivel Jean-Charles , Biancotto Angélique , Vanpouille Christophe , Origgi Francesco , Malnati Mauro S. , Schols Dominique , Lusso Paolo , Margolis Leonid B. 
Published: December 2006

ABSTRACT
Human immunodeficiency virus (HIV) infection is often accompanied by infection with other pathogens that affect the clinical course of HIV disease. Here, we identified another virus, human herpesvirus 7 (HHV-7) that interferes with HIV type 1 (HIV-1) replication in human lymphoid tissue, where critical events of HIV disease occur. Like the closely related HHV-6, HHV-7 suppresses the replication of CCR5-tropic (R5) HIV-1 in coinfected blocks of human lymphoid tissue. Unlike HHV-6, which affects HIV-1 by upregulating RANTES, HHV-7 did not upregulate any CCR5-binding chemokine. Rather, the inhibition of R5 HIV-1 by HHV-7 was associated with a marked downregulation of CD4, the cellular receptor shared by HHV-7 and HIV-1. HHV-7-induced CD4 downregulation was sufficient for HIV-1 inhibition, since comparable downregulation of CD4 with cyclotriazadisulfonamide, a synthetic macrocycle that specifically modulates expression of CD4, resulted in the suppression of HIV infection similar to that seen in HHV-7-infected tissues. In contrast to R5 HIV-1, CXCR4-tropic (X4) HIV-1 was only minimally suppressed by HHV-7 coinfection. This selectivity in suppression of R5 and X4 HIV-1 is explained by a suppression of HHV-7 replication in X4- but not in R5-coinfected tissues. These results suggest that HIV-1 and HHV-7 may interfere in lymphoid tissue in vivo, thus potentially affecting the progression of HIV-1 disease. Knowledge of the mechanisms of interaction of HIV-1 with HHV-7, as well as with other pathogens that modulate HIV-1 replication, may provide new insights into HIV pathogenesis and lead to the development of new anti-HIV therapeutic strategies.
Epstein-Barr Virus BZLF1 Gene, a Switch from Latency to Lytic Infection, Is Expressed as an Immediate-Early Gene after Primary Infection of B Lymphocytes
Authors: Wen Wangrong , Iwakiri Dai , Yamamoto Koji , Maruo Seiji , Kanda Teru , Takada Kenzo 
Published: December 2006

ABSTRACT
We demonstrate here that the Epstein-Barr virus (EBV) BZLF1 gene, a switch from latent infection to lytic infection, is expressed as early as 1.5 h after EBV infection in Burkitt's lymphoma-derived, EBV-negative Akata and Daudi cells and primary B lymphocytes. Since BZLF1 mRNA is expressed even when the cells are infected with EBV in the presence of anisomycin, an inhibitor of protein synthesis, its expression does not require prerequisite protein synthesis, indicating that BZLF1 is expressed as an immediate-early gene following primary EBV infection of B lymphocytes.
Mouse Hepatitis Virus Does Not Induce Beta Interferon Synthesis and Does Not Inhibit Its Induction by Double-Stranded RNA
Authors: Zhou Haixia , Perlman Stanley 
Published: December 2006

ABSTRACTMouse hepatitis virus (MHV) does not induce interferon (IFN) production in fibroblasts or bone marrow-derived dendritic cells. In this report, we show that the essential IFN-β transcription factors NF-κB and IFN regulatory factor 3 are not activated for nuclear translocation and gene induction during infection. However, MHV was unable to inhibit the activation of these factors and subsequent IFN-β production induced by poly(I:C). Further, MHV infection did not inhibit IFN-β production mediated by known host pattern recognition receptors (PRRs) (RIG-I, Mda-5, and TLR3). These results are consistent with the notion that double-stranded RNA, produced during MHV infection, is not accessible to cellular PRRs.
Inefficient Human Immunodeficiency Virus Replication in Mobile Lymphocytes
Authors: Sourisseau Marion , Sol-Foulon Nathalie , Porrot Françoise , Blanchet Fabien , Schwartz Olivier 
Published: December 2006

ABSTRACT
Cell-to-cell viral transfer facilitates the spread of lymphotropic retroviruses such as human immunodeficiency virus (HIV) and human T-cell leukemia virus (HTLV), likely through the formation of “virological synapses” between donor and target cells. Regarding HIV replication, the importance of cell contacts has been demonstrated, but this phenomenon remains only partly characterized. In order to alter cell-to-cell HIV transmission, we have maintained cultures under continuous gentle shaking and followed viral replication in this experimental system. In lymphoid cell lines, as well as in primary lymphocytes, viral replication was dramatically reduced in shaken cultures. To document this phenomenon, we have developed an assay to assess the relative contributions of free and cell-associated virions in HIV propagation. Acutely infected donor cells were mixed with carboxyfluorescein diacetate succinimidyl ester-labeled lymphocytes as targets, and viral production was followed by measuring HIV Gag expression at different time points by flow cytometry. We report that cellular contacts drastically enhance productive viral transfer compared to what is seen with infection with free virus. Productive cell-to-cell viral transmission required fusogenic viral envelope glycoproteins on donor cells and adequate receptors on targets. Only a few syncytia were observed in this coculture system. Virus release from donor cells was unaffected when cultures were gently shaken, whereas virus transfer to recipient cells was severely impaired. Altogether, these results indicate that cell-to-cell transfer is the predominant mode of HIV spread and help to explain why this virus replicates so efficiently in lymphoid organs.
Assembly of Two Independent Populations of Flock House Virus Particles with Distinct RNA Packaging Characteristics in the Same Cell
Authors: Venter P. Arno , Schneemann Anette 
Published: December 2006

ABSTRACT

Flock House virus
(FHV;
Nodaviridae
) is a positive-strand RNA virus that encapsidates a bipartite genome consisting of RNA1 and RNA2. We recently showed that specific recognition of these RNAs for packaging into progeny particles requires coat protein translated from replicating viral RNA. In the present study, we investigated whether the entire assembly pathway, i.e., the formation of the initial nucleating complex and the subsequent completion of the capsid, is restricted to the same pool of coat protein subunits. To test this, coat proteins carrying either FLAG or hemagglutinin epitopes were synthesized from replicating or nonreplicating RNA in the same cell, and the resulting particle population and its RNA packaging phenotype were analyzed. Results from immunoprecipitation analysis and ion-exchange chromatography showed that the differentially tagged proteins segregated into two distinct populations of virus particles with distinct RNA packaging phenotypes. Particles assembled from coat protein that was translated from replicating RNA contained the FHV genome, whereas particles assembled from coat protein that was translated from nonreplicating mRNA contained random cellular RNA. These data demonstrate that only coat proteins synthesized from replicating RNA partake in the assembly of virions that package the viral genome and that RNA replication, coat protein translation, and virion assembly are processes that are tightly coupled during the life cycle of FHV.
Suppression of Coronavirus Replication by Inhibition of the MEK Signaling Pathway
Authors: Cai Yingyun , Liu Yin , Zhang Xuming 
Published: December 2006

ABSTRACT

We previously demonstrated that infection of cultured cells with murine coronavirus mouse hepatitis virus (MHV) resulted in activation of the mitogen-activated protein kinase (Raf/MEK/ERK) signal transduction pathway (Y. Cai et al., Virology 355:152-163, 2006). Here we show that inhibition of the Raf/MEK/ERK signaling pathway by the MEK inhibitor UO126 significantly impaired MHV progeny production (a reduction of 95 to 99% in virus titer), which correlated with the phosphorylation status of ERK1/2. Moreover, knockdown of MEK1/2 and ERK1/2 by small interfering RNAs suppressed MHV replication. The inhibitory effect of UO126 on MHV production appeared to be a general phenomenon since the effect was consistently observed in all six different MHV strains and in three different cell types tested; it was likely exerted at the postentry steps of the virus life cycle because the virus titers were similarly inhibited from infected cells treated at 1 h prior to, during, or after infection. Furthermore, the treatment did not affect the virus entry, as revealed by the virus internalization assay. Metabolic labeling and reporter gene assays demonstrated that translation of cellular and viral mRNAs appeared unaffected by UO126 treatment. However, synthesis of viral genomic and subgenomic RNAs was severely suppressed by UO126 treatment, as demonstrated by a reduced incorporation of [
3
H]uridine and a decrease in chloramphenicol acetyltransferase (CAT) activity in a defective-interfering RNA-CAT reporter assay. These findings indicate that the Raf/MEK/ERK signaling pathway is involved in MHV RNA synthesis.
Adenovirus Ubiquitin-Protein Ligase Stimulates Viral Late mRNA NuclearExport
Authors: Woo Jennifer L. , Berk Arnold J. 
Published: December 2006

ABSTRACT

Theadenovirus type 5 (Ad5) E1B-55K and E4orf6 proteins are required
together to stimulate viral late nuclear mRNA export to the cytoplasm
and to restrict host cell nuclear mRNA export during the late phase of
infection. Previous studies have shown that these two viral proteins
interact with the cellular proteins elongins B and C,
cullin 5, RBX1, and additional cellular proteins to form an E3
ubiquitin-protein ligase that polyubiquitinates p53 and probably one or
more subunits of the MRE11-RAD50-NBS1 (MRN) complex, directing their
proteasomal degradation. The MRN complex is required for cellular DNA
double-strand break repair and induction of the DNA damage response by
adenovirus infection. To determine if the ability of E1B-55K and E4orf6
to stimulate viral late mRNA nuclear export requires the
ubiquitin-protein ligase activity of this viral ubiquitin-protein
ligase complex, we designed and expressed a dominant-negative mutant
form of cullin 5 in HeLa cells before infection with wild-type Ad5 or
the E1B-55K null mutant
dl
1520. The dominant-negative cullin 5
protein stabilized p53 and the MRN complex, indicating that it
inhibited the viral ubiquitin-protein ligase but had no effect on viral
early mRNA synthesis, early protein synthesis, or viral DNA
replication. However, expression of the dominant-negative cullin 5
protein caused a decrease in viral late protein synthesis and viral
nuclear mRNA export similar to the phenotype produced by mutations in
E1B-55K. We conclude that the stimulation of adenovirus late mRNA
nuclear export by E1B-55K and E4orf6 results from the ubiquitin-protein
ligase activity of the adenovirus ubiquitin-protein ligase
complex.
Mechanisms of Gastrointestinal CD4+T-Cell Depletion during Acuteand Early Human Immunodeficiency Virus Type 1 Infection
Authors: Mehandru Saurabh , Poles Michael A. , Tenner-Racz Klara , Manuelli Victoria , Jean-Pierre Patrick , Lopez Peter , Shet Anita , Low Andrea , Mohri Hiroshi , Boden Daniel , Racz Paul , Markowitz Martin 
Published: December 2006

ABSTRACTDuring acute and early human immunodeficiency virus type 1 (HIV-1) infection (AEI) more than 50% of CD4+T cells are preferentially depleted from the gastrointestinal (GI) lamina propria. To better understand the underlying mechanisms, we studied virological and immunological events within the peripheral blood (PB) and GI tract during AEI. A total of 32 AEI subjects and 18 uninfected controls underwent colonic biopsy. HIV-1 viral DNA and RNA levels were quantified in CD4+T cells derived from the GI tract and PB by using real-time PCR. The phenotype of infected cells was characterized by using combinations of immunohistochemistry and in situ hybridization. Markers of immunological memory, activation, and proliferation were examined by flow cytometry and immunohistochemistry, and the host-derived cytotoxic cellular response was examined by using immunohistochemistry. GI CD4+T cells harbored, on average, 13-fold higher HIV-1 viral DNA levels and 10-fold higher HIV-1 RNA levels than PB CD4+T cells during AEI. HIV-1 RNA was detected in both “activated” and“ nonactivated” mucosal CD4+T cells. A significantly higher number of activated and proliferating T cells were detected in the GI tract compared to the PB, and a robust cytotoxic response (HIV-1 specificity not determined) was detected in the GI tract as early as 18 days postinfection. Mucosal CD4+T-cell depletion is multifactorial. Direct viral infection likely accounts for the earliest loss of CD4+T cells. Subsequently, ongoing infection of susceptible CD4+T cells, along with activation-induced cellular death and host cytotoxic cellular response, are responsible for the persistence of the lesion.
Evidence for Persistent, Occult Infection in Neonatal Macaques following Perinatal Transmission of Simian-Human Immunodeficiency Virus SF162P3
Authors: Jayaraman Pushpa , Zhu Tuofu , Misher Lynda , Mohan Deepika , Kuller LaRene , Polacino Patricia , Richardson Barbra A. , Bielefeldt-Ohmann Helle , Anderson David , Hu Shiu-Lok , Haigwood Nancy L. 
Published: December 2006

ABSTRACT

To model human immunodeficiency virus (HIV) perinatal transmission, we studied infection of simian-human immunodeficiency virus (SHIV) SF162P3 in 10 pregnant
Macaca nemestrina
females and their offspring. Four of nine infants born to and suckled by these dams had evidence of infection, a transmission rate of 44.4% (95% confidence interval, 13.7% to 78.8%). We quantified transplacentally acquired and de novo Env-specific immunoglobulin G (IgG), IgM, and neutralizing antibodies in newborns. Transmission of escape variants was confirmed. In utero infection (
n
= 1) resulted in high viremia, depletion of peripheral CD4
+
T cells, and rapid evolution of
env
in blood and tissues. Peripartum or postpartum SHIV infection (
n
= 3) resulted in postacute viral control that was undetectable by very sensitive multiplex PCR, despite increasing antibodies. Seropositive infants with highly controlled viremia had homogeneous peripheral blood
env
sequences, and their tissues had <3 copies per million cells. A high incidence of seropositive virus-low or -negative SHIV infection in infant macaques has implications for HIV type 1 perinatal transmission and detection.
The Switch from Latent to Productive Infection in Epstein-Barr Virus-Infected B Cells Is Associated with Sensitization to NK Cell Killing
Authors: Pappworth Isabel Y. , Wang Eddie C. , Rowe Martin 
Published: December 2006

ABSTRACTFollowing activation of Epstein-Barr virus (EBV)-infected B cells from latent to productive (lytic) infection, there is a concomitant reduction in the level of cell surface major histocompatibility complex (MHC) class I molecules and an impaired antigen-presenting function that may facilitate evasion from EBV-specific CD8+cytotoxic T cells. In some other herpesviruses studied, most notably human cytomegalovirus (HCMV), evasion of virus-specific CD8+effector responses via downregulation of surface MHC class I molecules is supplemented with specific mechanisms for evading NK cells. We now report that EBV differs from HCMV in this respect. While latently infected EBV-positive B cells were resistant to lysis by two NK lines and by primary polyclonal NK cells from peripheral blood, these effectors efficiently killed cells activated into the lytic cycle. Susceptibility to NK lysis coincided not only with downregulation of HLA-A, -B, and -C molecules that bind to the KIR family of inhibitory receptors on NK cells but also with downregulation of HLA-E molecules binding the CD94/NKG2A inhibitory receptors. Conversely, ULBP-1 and CD112, ligands for the NK cell-activating receptors NKG2D and DNAM-1, respectively, were elevated. Susceptibility of the virus-producing target cells to NK cell lysis was partially reversed by blocking ULBP-1 or CD112 with specific antibodies. These results highlight a fundamental difference between EBV and HCMV with regards to evasion of innate immunity.
C5 Modulates Airway Hyperreactivity and Pulmonary Eosinophilia during Enhanced Respiratory Syncytial Virus Disease by Decreasing C3a Receptor Expression
Authors: Melendi Guillermina A. , Hoffman Scott J. , Karron Ruth A. , Irusta Pablo M. , Laham Federico R. , Humbles Alison , Schofield Brian , Pan Chien-Hsiung , Rabold Richard , Thumar Bhagvanji , Thumar Adeep , Gerard Norma P. , Mitzner Wayne , Barnum Scott R. , Gerard Craig , Kleeberger Steven R. , Polack Fernando P. 
Published: December 2006

ABSTRACTEnhanced respiratory syncytial virus disease, a serious pulmonary disorder that affected recipients of an inactivated vaccine against respiratory syncytial virus in the 1960s, has delayed the development of vaccines against the virus. The enhanced disease was characterized by immune complex-mediated airway hyperreactivity and a severe pneumonia associated with pulmonary eosinophilia. In this paper, we show that complement factors contribute to enhanced-disease phenotypes. Mice with a targeted disruption of complement component C5 affected by the enhanced disease displayed enhanced airway reactivity, lung eosinophilia, and mucus production compared to wild-type mice and C5-deficient mice reconstituted with C5. C3aR expression in bronchial epithelial and smooth muscle cells in the lungs of C5-deficient mice was enhanced compared to that in wild-type and reconstituted rodents. Treatment of C5-deficient mice with a C3aR antagonist significantly attenuated airway reactivity, eosinophilia, and mucus production. These results indicate that C5 plays a crucial role in modulating the enhanced-disease phenotype, by affecting expression of C3aR in the lungs. These findings reveal a novel autoregulatory mechanism for the complement cascade that affects the innate and adaptive immune responses.
Tubulovesicular Structures within Vesicular Stomatitis Virus G Protein-Pseudotyped Lentiviral Vector Preparations Carry DNA and Stimulate Antiviral Responses via Toll-Like Receptor 9
Authors: Pichlmair Andreas , Diebold Sandra S. , Gschmeissner Stephen , Takeuchi Yasuhiro , Ikeda Yasuhiro , Collins Mary K. , Reis e Sousa Caetano 
Published: December 2006

ABSTRACT
Recombinant lentiviral vectors (LVs) are commonly used as research tools and are being tested in the clinic as delivery agents for gene therapy. Here, we show that Vesicular stomatitis virus G protein (VSV-G)-pseudotyped LV preparations produced by transient transfection are heavily contaminated with tubulovesicular structures (TVS) of cellular origin, which carry nucleic acids, including the DNA plasmids originally used for LV generation. The DNA carried by TVS can act as a stimulus for innate antiviral responses, triggering Toll-like receptor 9 and inducing alpha/beta interferon production by plasmacytoid dendritic cells (pDC). Removal of TVS markedly reduces the ability of VSV-G-pseudotyped LV preparations to activate pDC. Conversely, virus-free TVS are sufficient to stimulate pDC and act as potent adjuvants in vivo, eliciting T- and B-cell responses to coadministered proteins. These results highlight the role of by-products of virus production in determining the immunostimulatory properties of recombinant virus preparations and suggest possible strategies for diminishing responses to LVs in gene therapy and in research use.