bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytotoxic T-Lymphocyte Epitope Immunodominance in the Control of Choroid Plexus Tumors in Simian Virus 40 Large T Antigen Transgenic Mice
Authors: Schell Todd D. , Mylin Lawrence M. , Georgoff Ingo , Teresky Angelica K. , Levine Arnold J. , Tevethia Satvir S. 
Published: December 2019

ABSTRACTThe simian virus 40 (SV40) large tumor antigen (Tag) is a virus-encoded oncoprotein which is the target of a strong cytotoxic T-lymphocyte (CTL) response. Three immunodominant H-2b-restricted epitopes, designated epitopes I, II/III, and IV, have been defined. We investigated whether induction of CTLs directed against these Tag epitopes might control Tag-induced tumors in SV11+(H-2b) mice. SV11+mice develop spontaneous tumors of the choroid plexus due to expression of SV40 Tag as a transgene. We demonstrate that SV11+mice are functionally tolerant to the immunodominant Tag CTL epitopes. CTLs specific for the H-2Kb-restricted Tag epitope IV were induced in SV11+mice following adoptive transfer with unprimed C57BL/6 spleen cells and immunization with recombinant vaccinia viruses expressing either full-length Tag or the H-2Kb-restricted epitope IV as a minigene. In addition, irradiation of SV11+mice prior to adoptive transfer with unprimed C57BL/6 spleen cells led to the priming of epitope IV-specific CTLs by the endogenous Tag. Induction of epitope IV-specific CTLs in SV11+mice by either approach correlated with increased life span and control of the choroid plexus tumor progression, indicating that CTLs specific for the immunodominant Tag epitope IV control the progressive growth of spontaneous tumors induced by this DNA virus oncogene in transgenic mice.
Induction of Adult T-Cell Leukemia-Like Lymphoproliferative Disease and Its Inhibition by Adoptive Immunotherapy in T-Cell-Deficient Nude Rats Inoculated with Syngeneic Human T-Cell Leukemia Virus Type 1-Immortalized Cells
Authors: Ohashi Takashi , Hanabuchi Shino , Kato Hirotomo , Koya Yoshihiro , Takemura Fumiyo , Hirokawa Katsuiku , Yoshiki Takashi , Tanaka Yuetsu , Fujii Masahiro , Kannagi Mari 
Published: December 2019

ABSTRACTHuman T-cell leukemia virus type 1 (HTLV-1) has been shown to be the etiologic agent of adult T-cell leukemia (ATL), but the in vivo mechanism by which the virus causes the malignant transformation is largely unknown. In order to investigate the mechanisms of HTLV-1 leukemogenesis, we developed a rat model system in which ATL-like disease was reproducibly observed, following inoculation of various rat HTLV-1-immortalized cell lines. When previously established cell lines, F344-S1 and TARS-1, but not TART-1 or W7TM-1, were inoculated, systemic multiple tumor development was observed in adult nude (nu/nu) rats. FPM1 cells, newly established from a heterozygous (nu/+) rat syngeneic tonu/nurats, caused transient tumors only at the injection site in adultnu/nurats, but could progressively grow in newbornnu/nurats and metastasize in lymph nodes. The derivative cell line (FPM1-V1AX) serially passed through newbornnu/nurats acquired the potency to grow in adultnu/nurats. These results indicated that only some with additional changes but not all of the in vitro HTLV-1-immortalized cell lines possessed in vivo tumorigenicity. Using the syngeneic system, we further showed the inhibition of tumor development by transferring splenic T cells from immunized rats, suggesting the involvement of T cells in the regression of tumors. This novel and reproducible nude rat model of human ATL would be useful for investigation of leukemogenesis and antitumor immune responses in HTLV-1 infection.
Association of JC Virus Large T Antigen with Myelin Basic Protein Transcription Factor (MEF-1/Purα) in Hypomyelinated Brains of Mice Transgenically Expressing T Antigen
Authors: Tretiakova Anna , Otte Jessica , Croul Sidney E. , Kim Julie H. , Johnson Edward M. , Amini Shohreh , Khalili Kamel 
Published: December 2019

ABSTRACT
Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease caused by cytolytic destruction of oligodendrocytes, the myelin-producing cells of the central nervous system, by the human neurotropic JC virus (JCV). The early protein of JCV, T antigen, which is produced at the early stage of infection, is important for orchestrating the events leading to viral lytic infection and cytolytic destruction of oligodendrocytes. Results from transgenic mouse studies, however, have revealed that, in the absence of lytic infection, this protein can induce brain hypomyelination and suppression of myelin gene expression. Since expression of the gene encoding myelin basic protein, the major component of myelin, can be regulated by a DNA-binding transcription factor, MEF-1/Purα, (Purα), we have examined the level of this protein in transgenic mouse brains. Results from immunoprecipitation and Western blots showed that while there was no drastic decrease in the level of MEF-1/Purα in transgenic mouse brains, JCV T antigen was found in a complex with MEF-1/Purα. Immunohistological studies revealed abnormal oligodendrocytes in white matter, where MEF-1/Purα and T antigen were detected. Furthermore, immunogold electron microscopic studies revealed that Purα and T antigen are colocalized in the nucleus of the oligodendrocytes and in hippocampal neurons. Interestingly, results from cell culture studies revealed that incubation of oligodendrocytes with JCV led to a drastic decrease in the level of MEF-1/Purα protein. These observations provide insight into the molecular pathogenesis of PML and support a model for a dual effect of JCV on inducing hypomyelination by (i) affecting myelin gene expression via interaction of JCV T antigen and the myelin gene transcription factor, MEF-1/Purα, and (ii) causing a decline in the level of the host regulatory proteins, including MEF-1/Purα, which are involved in myelin gene expression.
Transduction of Well-Differentiated Airway Epithelium by Recombinant Adeno-Associated Virus Is Limited by Vector Entry
Authors: Bals Robert , Xiao Weidong , Sang Nianli , Weiner Daniel J. , Meegalla Rupalie L. , Wilson James M. 
Published: December 2019

ABSTRACT
The limitations of adeno-associated virus (AAV)-mediated vectors for lung-directed gene transfer were investigated by using differentiated human respiratory epithelium in air-liquid interface cultures. Transduction efficiency was high in undifferentiated cells and was enhanced in well-differentiated cells after basolateral application of the vector or after apical application following disruption of tight junctions or pretreatment of the cultures with glycosidases. These results indicate that transduction of airway epithelia by AAV vectors is limited by entry and reinforce the importance of a physical barrier on the airway surface.
Dengue Virus Type 1 Nonstructural Glycoprotein NS1 Is Secreted from Mammalian Cells as a Soluble Hexamer in a Glycosylation-Dependent Fashion
Authors: Flamand Marie , Megret Françoise , Mathieu Magali , Lepault Jean , Rey Félix A. , Deubel Vincent 
Published: December 2019

ABSTRACT

Nonstructural glycoprotein NS1, specified by dengue virus type 1 (Den-1), is secreted from infected green monkey kidney (Vero) cells in a major soluble form characterized by biochemical and biophysical means as a unique hexameric species. This noncovalently bound oligomer is formed by three dimeric subunits and has a molecular mass of 310 kDa and a Stokes radius of 64.4 Å. During protein export, one of the two oligosaccharides of NS1 is processed into an endo-β-
N
-acetylglucosaminidase F-resistant complex-type sugar while the other remains of the polymannose type, protected in the dimeric subunit from the action of maturation enzymes. Complete processing of the complex-type sugar appears to be required for efficient release of soluble NS1 into the culture fluid of infected cells, as suggested by the repressive effects of the N-glycan processing inhibitors swainsonine and deoxymannojyrimicin. These results, together with observations related to the absence of secretion of NS1 from Den-infected insect cells, suggest that maturation and secretion of hexameric NS1 depend on the glycosylation status of the host cell.
Retroviral Vectors Pseudotyped with Lymphocytic Choriomeningitis Virus
Authors: Miletic Hrvoje , Bruns Michael , Tsiakas Konstantinos , Vogt Birgit , Rezai Roya , Baum Christopher , Kühlke Klaus , Cosset François-Loïc , Ostertag Wolfram , Lother Heinz , von Laer Dorothee 
Published: December 2019

ABSTRACT
Pseudotyping can improve retroviral vector stability and transduction efficiency. Here, we describe a novel pseudotype of murine leukemia virus packaged with lymphocytic choriomeningitis virus (LCMV). This pseudotype was stable during ultracentrifugation and infected several cell lines from different species. Moreover, LCMV glycoproteins were not cell toxic.
Frequency and Stability of Chromosomal Integration of Adenovirus Vectors
Authors: Harui Airi , Suzuki Shinobu , Kochanek Stefan , Mitani Kohnosuke 
Published: December 2019

ABSTRACTOne of the limitations of adenovirus vectors is the lack of machinery necessary for their integration into host chromosomes, resulting in short-term gene expression in dividing cells. We analyzed frequencies of integration and persistence of gene expression from integrated adenovirus vectors. Both E1-substituted and helper-dependent adenovirus vectors achieved similar integration efficiencies of ∼10−3to 10−5per cell, with the helper-dependent vector showing slightly higher efficiencies. In stable cell pools, gene expression of the integrated vector persisted for at least 50 cell divisions without selection. However, some stable cell clones showed changes in gene expression, which were accompanied by structural changes in the integrated vector DNA.
Common Neutralization Epitope in Minor Capsid Protein L2 of Human Papillomavirus Types 16 and 6
Authors: Kawana Kei , Yoshikawa Hiroyuki , Taketani Yuji , Yoshiike Kunito , Kanda Tadahito 
Published: December 2019

ABSTRACT
Studies of virus neutralization by antibody are a prerequisite for development of a prophylactic vaccine strategy against human papillomaviruses (HPVs). Using HPV16 and -6 pseudovirions capable of inducing β-galactosidase in infected monkey COS-1 cells, we examined the neutralizing activity of mouse monoclonal antibodies (MAbs) that recognize surface epitopes in HPV16 minor capsid protein L2. Two MAbs binding to a synthetic peptide with the HPV16 L2 sequence of amino acids (aa) 108 to 120 were found to inhibit pseudoinfections with HPV16 as well as HPV6. Antisera raised by immunizing BALB/c mice with the synthetic peptide had a cross-neutralizing activity similar to that of the MAb. The data indicate that HPV16 and -6 have a common cross-neutralization epitope (located within aa 108 to 120 of L2 in HPV16), suggesting that this epitope may be shared by other genital HPVs.
Reappearance of Founder Virus Sequence in Human Immunodeficiency Virus Type 1-Infected Patients
Authors: Karlsson Annika C. , Gaines Hans , Sällberg Matti , Lindbäck Stefan , Sönnerborg Anders 
Published: December 2019

ABSTRACT
Different patterns of temporal evolution in human immunodeficiency virus type 1 V3 and p17 regions are described for eight patients studied during the first years following primary infection. In samples from three patients, a rapid replacement of the major sequence occurred but the original sequence reappeared later simultaneously with clinical deterioration and increased plasma viral load.
Characterization of Hepatitis C Virus E2 Glycoprotein Interaction with a Putative Cellular Receptor, CD81
Authors: Flint Mike , Maidens Catherine , Loomis-Price Larry D. , Shotton Christine , Dubuisson Jean , Monk Peter , Higginbottom Adrian , Levy Shoshana , McKeating Jane A. 
Published: December 2019

ABSTRACTA truncated soluble form of the hepatitis C virus E2 glycoprotein, E2661, binds specifically to the surface of cells expressing human CD81 (hCD81) but not other members of the tetraspanin family (CD9, CD63, and CD151). No differences were noted between the level of E2661binding to hCD81 expressed on the surface of rat RBL or KM3 cells compared to Daudi and Molt-4 cells, suggesting that additional human-cell-specific factors are not required for the primary interaction of E2 with the cell surface. E2 did not interact with African green monkey (AGM) CD81 on the surface of COS cells, which differs from the hCD81 sequence at four residues within the second extracellular region (EC2) (amino acids [aa] 163, 186, 188, and 196), suggesting that one or more of these residues defines the site of interaction with E2. Various recombinant forms of CD81 EC2 show differences in the ability to bind E2, suggesting that CD81 conformation is important for E2 recognition. Regions of E2 involved in the CD81 interaction were analyzed, and our data suggest that the binding site is of a conformational nature involving aa 480 to 493 and 544 to 551 within the E2 glycoprotein. Finally, we demonstrate that ligation of CD81 by E2661induced aggregation of lymphoid cells and inhibited B-cell proliferation, demonstrating that E2 interaction with CD81 can modulate cell function.
Attenuated, Replication-Competent Herpes Simplex Virus Type 1 Mutant G207: Safety Evaluation of Intracerebral Injection in Nonhuman Primates
Authors: Hunter William D. , Martuza Robert L. , Feigenbaum Frank , Todo Tomoki , Mineta Toshihiro , Yazaki Takahito , Toda Masahiro , Newsome Joseph T. , Platenberg R. Craig , Manz Herbert J. , Rabkin Samuel D. 
Published: December 2019

ABSTRACT

This study examined the safety of intracerebral inoculation of G207, an attenuated, replication-competent herpes simplex virus type 1 (HSV-1) recombinant, in nonhuman primates. Sixteen New World owl monkeys (
Aotus nancymae
[karyotype 1, formerly believed to be
A. trivirgatus
]), known for their exquisite susceptibility to HSV-1 infection, were evaluated. Thirteen underwent intracerebral inoculation with G207 at doses of 10
7
or 10
9
PFU, two were vehicle inoculated, and one served as an infected wild-type control and received 10
3
PFU of HSV-1 strain F. HSV-1 strain F caused rapid mortality and symptoms consistent with HSV encephalitis, including fever, hemiparesis, meningitis, and hemorrhage in the basal ganglia. One year after G207 inoculation, seven of the animals were alive and exhibited no evidence of clinical complications. Three deaths resulted from nonneurologic causes unrelated to HSV infection, and three animals were sacrificed for histopathologic examination. Two animals were reinoculated with G207 (10
7
PFU) at the same stereotactic coordinates 1 year after the initial G207 inoculation. These animals were alive and healthy 2 years after the second inoculation. Cerebral magnetic resonance imaging studies performed both before and after G207 inoculation failed to reveal radiographic evidence of HSV-related sequelae. Despite the lack of outwardly observable HSV pathology, measurable increases in serum anti-HSV titers were detected. Histopathological examination of multiple organ tissues found no evidence of HSV-induced histopathology or dissemination. We conclude that intracerebral inoculation of up to 10
9
PFU of G207, well above the efficacious dose in mouse tumor studies, is safe and therefore appropriate for human clinical trials.
The CC-Chemokine RANTES Increases the Attachment of Human Immunodeficiency Virus Type 1 to Target Cells via Glycosaminoglycans and Also Activates a Signal Transduction Pathway That Enhances Viral Infectivity
Authors: Trkola Alexandra , Gordon Cynthia , Matthews Jamie , Maxwell Elizabeth , Ketas Tom , Czaplewski Lloyd , Proudfoot Amanda E. I. , Moore John P. 
Published: December 2019

ABSTRACTWe have studied the mechanisms by which the CC-chemokine RANTES can enhance the infectivities of human immunodeficiency virus type 1 (HIV-1) and other enveloped viruses, when present at concentrations in excess of 500 ng/ml in vitro. Understanding the underlying mechanisms might throw light on fundamental processes of viral infection, in particular for HIV-1. Our principal findings are twofold: firstly, that oligomers of RANTES can cross-link enveloped viruses, including HIV-1, to cells via glycosaminoglycans (GAGs) present on the membranes of both virions and cells; secondly, that oligomers of RANTES interact with cell-surface GAGs to transduce a herbimycin A-sensitive signal which, over a period of several hours, renders the cells more permissive to infection by several viruses, including HIV-1. The enhancement mechanisms require that RANTES oligomerize either in solution or following binding to GAGs, since no viral infectivity enhancement is observed with a mutant form of the RANTES molecule that contains a single-amino-acid change (glutamic acid to serine at position 66) which abrogates oligomerization.
Proteolytic Activity, the Carboxy Terminus of Gag, and the Primer Binding Site Are Not Required for Pol Incorporation into Foamy Virus Particles
Authors: Baldwin David N. , Linial Maxine L. 
Published: December 2019

ABSTRACT
Human foamy virus (HFV) is the prototype member of the spumaviruses. While similar in genomic organization to other complex retroviruses, foamy viruses share several features with their more distant relatives, the hepadnaviruses such as human hepatitis B virus (HBV). Both HFV and HBV express their Pol proteins independently from the structural proteins. However unlike HBV, Pol is not required for assembly of HFV core particles or for packaging of viral RNA. These results suggest that the assembly of Pol into HFV particles must occur by a mechanism different from those used by retroviruses and hepadnaviruses. We have examined possible mechanisms for HFV Pol incorporation, including the role of proteolysis in assembly of Pol and the role of initiation of reverse transcription. We have found that proteolytic activity is not required for Pol incorporation. p4 Gag and the residues immediately upstream of the cleavage site in Gag are also not important. Deletion of the primer binding site had no effect on assembly, ruling out early steps of reverse transcription in the process of Pol incorporation.
Human Immunodeficiency Virus Type 1 Strains R5 and X4 Induce Different Pathogenic Effects in hu-PBL-SCID Mice, Depending on the State of Activation/Differentiation of Human Target Cells at the Time of Primary Infection
Authors: Fais Stefano , Lapenta Caterina , Santini Stefano M. , Spada Massimo , Parlato Stefania , Logozzi Mariantonia , Rizza Paola , Belardelli Filippo 
Published: December 2019

ABSTRACTIn a previous study, we had found that the extent of T-cell dysfunctions induced by a T-tropic strain of human immunodeficiency virus type 1 (HIV-1) in SCID mice reconstituted with human peripheral blood lymphocytes (hu-PBLs) (hu-PBL-SCID mice) was related to the in vivo state of activation of the human lymphocytes. In this article, we compared the effect of infection of hu-PBL-SCID mice with either T-tropic (X4) or M-tropic (R5) strains of HIV-1 by performing virus inoculation at either 2 h or 2 weeks after the hu-PBL transfer, when the human T cells exhibited a marked activation state or a predominant memory phenotype, respectively. A comparable level of infection was found when hu-PBL-SCID mice were challenged with either the SF162 R5 or the IIIB X4 strain of HIV at 2 h postreconstitution, while at 2 weeks, the R5 virus infection resulted in a higher level of HIV replication than the X4 virus. The R5 strain induced a marked human CD4+T-cell depletion along with a drop in levels of human immunoglobulin M in serum and release of soluble factors at both infection times, while the X4 virus induced severe immune dysfunctions only at 2 h. Of interest, injection of hu-PBLs into SCID mice resulted in a marked up-regulation of CCR5 on human CD4+T cells. The percentage of CXCR4+cells did not change after transplantation, even though a significant decrease in antigen expression was observed. Comparative experiments with two molecular clones of HIV-1 (X4 SF2 and R5 SF162) and two envelope recombinant viruses generated from these viruses showed that R5 viruses (SF162 and the chimeric env-SF162-SF2) caused an extensive depletion of human CD4+T cells in SCID mice at both 2 h and 2 weeks after reconstitution, while the X4 viruses (SF2 and the chimeric env-SF2-SF162) induced CD4 T-cell depletion only when infection was performed at the 2-h reconstitution time. These results emphasize the importance of the state of activation/differentiation of human CD4+T cells and gp120-coreceptor interactions at the time of primary infection in determining HIV-1 pathogenicity in the hu-PBL-SCID mouse model.
Characterization of CELO Virus Proteins That Modulate the pRb/E2F Pathway
Authors: Lehrmann Heike , Cotten Matt 
Published: December 2019

ABSTRACT
The avian adenovirus CELO can, like the human adenoviruses, transform several mammalian cell types, yet it lacks sequence homology with the transforming, early regions of human adenoviruses. In an attempt to identify how CELO virus activates the E2F-dependent gene expression important for S phase in the host cell, we have identified two CELO virus open reading frames that cooperate in activating an E2F-inducible reporter system. The encoded proteins, GAM-1 and Orf22, were both found to interact with the retinoblastoma protein (pRb), with Orf22 binding to the pocket domain of pRb, similar to other DNA tumor virus proteins, and GAM-1 interacting with pRb regions outside the pocket domain. The motif in Orf22 responsible for the pRb interaction is essential for Orf22-mediated E2F activation, yet it is remarkably unlike the E1A LxCxD and may represent a novel form of pRb-binding peptide.
Nonproductive Human Immunodeficiency Virus Type 1 Infection in Nucleoside-Treated G
0
Lymphocytes
Authors: Korin Yael D. , Zack Jerome A. 
Published: December 2019

ABSTRACT

Productive infection by human immunodeficiency virus type 1 (HIV-1) requires the activation of target cells. Infection of quiescent peripheral CD4 lymphocytes by HIV-1 results in incomplete, labile, reverse transcripts. We have previously identified G
1b
as the cell cycle stage required for the optimal completion of the reverse transcription process in T lymphocytes. However, the mechanism(s) involved in the blockage of reverse transcription remains undefined. In this study we investigated whether nucleotide levels influence viral reverse transcription in G
0
cells. For this purpose the role of the enzyme ribonucleotide reductase was bypassed, by adding exogenous deoxyribonucleosides to highly purified T cells in the G
0
or the G
1a
phase of the cell cycle. Our data showed a significant increase in the efficiency of the reverse transcription process following the addition of the deoxyribonucleosides. To define the stability and functionality of these full reverse transcripts, we used an HIV-1 reporter virus that expresses the murine heat-stable antigen on the surfaces of infected cells. Following activation of infected quiescent cells treated with exogenous nucleosides, no increased rescue of productive infection was seen. Thus, in addition to failure to complete reverse transcription, there was an additional nonreversible blockage of productive infection in quiescent T cells. These experiments have important relevance in the gene therapy arena, in terms of improving the ability of lentivirus vectors to enter metabolically inactive cells, such as hematopoietic stem cells.