bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Nucleotide Sequence and Spliced
pol
mRNA Levels of the Nonprimate Spumavirus Bovine Foamy Virus
Authors: Holzschu Donald L. , Delaney Mari A. , Renshaw Randall W. , Casey James W. 
Published: December 2019

ABSTRACT

We have determined the complete nucleotide sequence of a replication-competent clone of bovine foamy virus (BFV) and have quantitated the amount of splice
pol
mRNA processed early in infection. The 544-amino-acid Gag protein precursor has little sequence similarity with its primate foamy virus homologs, but the putative nucleocapsid (NC) protein, like the primate NCs, contains the three glycine-arginine-rich regions that are postulated to bind genomic RNA during virion assembly. The BFV
gag
and
pol
open reading frames overlap, with
pro
and
pol
in the same translational frame. As with the human foamy virus (HFV) and feline foamy virus, we have detected a spliced
pol
mRNA by PCR. Quantitatively, this mRNA approximates the level of full-length genomic RNA early in infection. The integrase (IN) domain of reverse transcriptase does not contain the canonical HH-CC zinc finger motif present in all characterized retroviral INs, but it does contain a nearby histidine residue that could conceivably participate as a member of the zinc finger. The
env
gene encodes a protein that is over 40% identical in sequence to the HFV Env. By comparison, the Gag precursor of BFV is predicted to be only 28% identical to the HFV protein.
Delayed Infection after Immunization with a Peptide from the Transmembrane Glycoprotein of the Feline Immunodeficiency Virus
Authors: Richardson J. , Moraillon A. , Crespeau F. , Baud S. , Sonigo P. , Pancino G. 
Published: December 2019

ABSTRACT
Recent advances in the quantitative assessment of viral burden, by permitting the extension of criteria applied to assess the efficacy of vaccines from all-or-none protection to diminution of the viral burden, may allow the identification of original immunogens of value in combined vaccines. Peptides corresponding to three domains of the envelope glycoproteins of feline immunodeficiency virus that are recognized during natural infection were used to immunize cats. After challenge with a primary isolate of feline immunodeficiency virus, the development of acute infection was monitored by quantitative assessment of the viral burden in plasma and tissues by competitive reverse transcription-PCR, by measurement of the humoral response developed to viral components, and by lymphocyte subset analysis. Whereas immunization with two peptides derived from the surface glycoprotein had no effect on the early course of infection, immunization with a peptide derived from the transmembrane glycoprotein delayed infection, as reflected by a diminished viral burden in the early phase of primary infection and delayed seroconversion. This peptide, located in the membrane-proximal region of the extracellular domain, has homology to an epitope of human immunodeficiency virus type 1 recognized by a broadly neutralizing monoclonal antibody. These results suggest that lentivirus transmembrane glycoproteins share a determinant in the juxtamembrane ectodomain which could be of importance in the design of vaccines against AIDS.
Application of a Fas Ligand Encoding a Recombinant Adenovirus Vector for Prolongation of Transgene Expression
Authors: Zhang Huang-Ge , Bilbao Guadalupe , Zhou Tong , Contreras Juan Luis , Gómez-Navarro Jesús , Feng Meizhen , Saito Izumu , Mountz John D. , Curiel David T. 
Published: December 2019

ABSTRACTAn adenovirus vector encoding murine Fas ligand (mFasL) under an inducible control was derived. In vivo ectopic expression of mFasL in murine livers induced an inflammatory cellular infiltration. Furthermore, ectopic expression of mFasL by myocytes did not allow prolonged vector-mediated transgene expression. Thus, ectopic expression of functional mFasL in vector-transduced cells does not appear to confer, by itself, an immunoprivileged site sufficient to mitigate adenovirus vector immunogenicity.
Autocrine Regulation and Experimental Modulation of Interleukin-6 Expression by Human Pulmonary Epithelial Cells Infected with Respiratory Syncytial Virus
Authors: Jiang Zili , Kunimoto Masaru , Patel Janak A. 
Published: December 2019

ABSTRACTThe mechanisms of regulation of interleukin-6 (IL-6) production in respiratory syncytial virus (RSV)-infected respiratory epithelial cells were evaluated in A549 cell cultures. Incubation with purified RSV resulted in significant production of IL-1α, IL-1β, IL-6, and tumor necrosis factor alpha (TNF-α). Addition of saturating concentrations of neutralizing antibodies against IL-1α, IL-1β, or TNF-α into purified RSV-infected cell cultures resulted in a significant inhibition of IL-6 production, although anti-IL-1α antibody had the most predominant effect (80% inhibition). Anti-IL-1α antibody also almost completely blocked the expression of mRNA for IL-6. Addition of therapeutic concentrations of dexamethasone (1 μM) or ribavirin (90 μg/ml), an antiviral agent, also significantly inhibited the synthesis of IL-6. Hence, in clinical settings, pharmacological agents such as the specific antagonists of IL-6-inducing cytokines, as well as dexamethasone and ribavirin, could be used to modulate IL-6 production.
Genetic Mapping of the Cloned Subgroup A Avian Sarcoma and Leukosis Virus Receptor Gene to the
TVA
Locus
Authors: Bates Paul , Rong Lijun , Varmus Harold E. , Young John A. T. , Crittenden Lyman B. 
Published: December 2019

ABSTRACT

A chicken gene conferring susceptibility to subgroup A avian sarcoma and leukosis viruses (ASLV-A) was recently identified by a gene transfer strategy. Classical genetic approaches had previously identified a locus,
TVA
, that controls susceptibility to ASLV-A. Using restriction fragment length polymorphism (RFLP) mapping in inbred susceptible (
TVA*S
) and resistant (
TVA*R
) chicken lines, we demonstrate that in 93 F
2
progeny an RFLP for the cloned receptor gene segregates with
TVA
. From these analyses we calculate that the cloned receptor gene lies within 5 centimorgans of
TVA
, making it highly probable that the cloned gene is the previously identified locus
TVA
. The polymorphism that distinguishes the two alleles of
TVA
in these inbred lines affects the encoded amino acid sequence of the region of Tva that encompasses the viral binding domain. However, analysis of the genomic sequence encoding this region of Tva in randomly bred chickens suggests that the altered virus binding domain is not the basis for genetic resistance in the chicken lines analyzed.
Mtv-1Superantigen Trafficks Independently of Major Histocompatibility Complex Class II Directly to the B-Cell Surface by the Exocytic Pathway
Authors: Grigg Michael E. , McMahon Christopher W. , Morkowski Stanislaw , Rudensky Alexander Y. , Pullen Ann M. 
Published: December 2019

ABSTRACTPresentation of theMtv-1superantigen (vSag1) to specific Vβ-bearing T cells requires association with major histocompatibility complex class II molecules. The intracellular route by which vSag1 trafficks to the cell surface and the site of vSag1-class II complex assembly in antigen-presenting B lymphocytes have not been determined. Here, we show that vSag1 trafficks independently of class II to the plasma membrane by the exocytic secretory pathway. At the surface of B cells, vSag1 associates primarily with mature peptide-bound class II αβ dimers, which are stable in sodium dodecyl sulfate. vSag1 is unstable on the cell surface in the absence of class II, and reagents that alter the surface expression of vSag1 and the conformation of class II molecules affect vSag1 stimulation of superantigen reactive T cells.
Effects of CCR5 and CD4 Cell Surface Concentrations on Infections by Macrophagetropic Isolates of Human Immunodeficiency Virus Type 1
Authors: Platt Emily J. , Wehrly Kathy , Kuhmann Shawn E. , Chesebro Bruce , Kabat David 
Published: December 2019

ABSTRACTIt has been proposed that changes in cell surface concentrations of coreceptors may control infections by human immunodeficiency virus type 1 (HIV-1), but the mechanisms of coreceptor function and the concentration dependencies of their activities are unknown. To study these issues and to generate stable clones of adherent cells able to efficiently titer diverse isolates of HIV-1, we generated two panels of HeLa-CD4/CCR5 cells in which individual clones express either large or small quantities of CD4 and distinct amounts of CCR5. The panels were made by transducing parental HeLa-CD4 cells with the retroviral vector SFF-CCR5. Derivative clones expressed a wide range of CCR5 quantities which were between 7.0 × 102and 1.3 × 105molecules/cell as measured by binding antibodies specific for CCR5 and the chemokine [125I]MIP1β. CCR5 was mobile in the membranes, as indicated by antibody-induced patching. In cells with a large amount of CD4, an unexpectedly low trace of CCR5 (between 7 × 102and 2.0 × 103molecules/cell) was sufficient for maximal susceptibility to all tested HIV-1, including primary patient macrophagetropic and T-cell-tropic isolates. Indeed, the titers as indicated by immunoperoxidase staining of infected foci were as high as the tissue culture infectious doses measured in human peripheral blood mononuclear cells. In contrast, cells with a small amount of CD4 required a much larger quantity of CCR5 for maximal infection by macrophagetropic HIV-1 (ca. 1.0 × 104to 2.0 × 104molecules/cell). Cells that expressed low and high amounts of CD4 were infected with equal efficiencies when CCR5 concentrations were above threshold levels for maximal infection. Our results suggest that the concentrations of CD4 and CCR5 required for efficient infections by macrophagetropic HIV-1 are interdependent and that the requirements for each are increased when the other component is present in a limiting amount. We conclude that CD4 and CCR5 directly or indirectly interact in a concentration-dependent manner within a pathway that is essential for infection by macrophagetropic HIV-1. In addition, our results suggest that multivalent virus-receptor bonds and diffusion in the membrane contribute to HIV-1 infections.
Recovery of a Fully Viable Chimeric Human Parainfluenza Virus (PIV) Type 3 in Which the Hemagglutinin-Neuraminidase and Fusion Glycoproteins Have Been Replaced by Those of PIV Type 1
Authors: Tao Tao , Durbin Anna P. , Whitehead Stephen S. , Davoodi Fatemah , Collins Peter L. , Murphy Brian R. 
Published: December 2019

ABSTRACT
The recent recovery of human parainfluenza virus type 3 (PIV3) from cDNA, together with the availability of a promising, highly characterized live attenuated PIV3 vaccine virus, suggested a novel strategy for the rapid development of comparable recombinant vaccine viruses for human PIV1 and PIV2. The strategy, illustrated here for PIV1, is to create chimeric viruses in which the two protective antigens, the hemagglutinin-neuraminidase (HN) and fusion (F) envelope glycoproteins, of an attenuated PIV3 variant are replaced by those of PIV1 or PIV2. As a first step, this has been achieved by using recombinant wild-type (wt) PIV3 as the recipient for PIV1 HN and F, engineered so that each PIV1 open reading frame is flanked by the existing PIV3 nontranslated regions and transcription signals. This yielded a viable chimeric recombinant virus, designated rPIV3-1, that encodes the PIV1 HN and F glycoproteins in the background of the wt PIV3 internal proteins. There were three noteworthy findings. First, in contrast to recently reported glycoprotein replacement chimeras of vesicular somatitis virus or measles virus, the PIV3-1 chimera replicates in LLC-MK2 cells and in the respiratory tract of hamsters as efficiently as its PIV1 and PIV3 parents. This is remarkable because the HN and F glycoproteins share only 43 and 47%, respectively, overall amino acid sequence identity between serotypes. In particular, the cytoplasmic tails share only 9 to 11% identity, suggesting that their presumed role in virion morphogenesis does not involve sequence-specific contacts. Second, rPIV3-1 was found to possess biological properties derived from each of its parent viruses. Specifically, it requires trypsin for efficient plaque formation in tissue culture, like its PIV1 parent but unlike PIV3. On the other hand, it causes an extensive cytopathic effect (CPE) in LLC-MK2 cultures which resembles that of its PIV3 parent but differs from that of its noncytopathic PIV1 parent. This latter finding indicates that the genetic basis for the CPE of PIV3 in tissue culture lies outside regions encoding the HN or F glycoprotein. Third, it should now be possible to rapidly develop a live attenuated PIV1 vaccine by the staged introduction of known, characterized attenuating mutations present in a live attenuated PIV3 vaccine candidate into the PIV3-1 cDNA followed by recovery of attenuated derivatives of rPIV3-1.
Type D Retrovirus Capsid Assembly and Release Are Active Events Requiring ATP
Authors: Weldon Robert A. , Parker William B. , Sakalian Michael , Hunter Eric 
Published: December 2019

ABSTRACTMason-Pfizer monkey virus (M-PMV), the prototype type D retrovirus, differs from most other retroviruses by assembling its Gag polyproteins into procapsids in the cytoplasm of infected cells. Once assembled, the procapsids migrate to the plasma membrane, where they acquire their envelope during budding. Because the processes of M-PMV protein transport, procapsid assembly, and budding are temporally and spatially unlinked, we have been able to determine whether cellular proteins play an active role during the different stages of procapsid morphogenesis. We report here that at least two stages of morphogenesis require ATP. Both procapsid assembly and procapsid transport to the plasma membrane were reversibly blocked by treating infected cells with sodium azide and 2-deoxy-d-glucose, which we show rapidly and reversibly depletes cellular ATP pools. Assembly of procapsids in vitro in a cell-free translation/assembly system was inhibited by the addition of nonhydrolyzable ATP analogs, suggesting that ATP hydrolysis and not just ATP binding is required. Since retrovirus Gag polyproteins do not bind or hydrolyze ATP, these results demonstrate that cellular components must play an active role during retrovirus morphogenesis.
Characterization of Ebola Virus Entry by Using Pseudotyped Viruses: Identification of Receptor-Deficient Cell Lines
Authors: Wool-Lewis Rouven J. , Bates Paul 
Published: December 2019

ABSTRACT

Studies analyzing Ebola virus replication have been severely hampered by the extreme pathogenicity of this virus. To permit analysis of the host range and function of the Ebola virus glycoprotein (Ebo-GP), we have developed a system for pseudotyping these glycoproteins into murine leukemia virus (MLV). This pseudotyped virus, MLV(Ebola), can be readily concentrated to titers which exceed 5 × 10
6
infectious units/ml and is effectively neutralized by antibodies specific for Ebo-GP. Analysis of MLV(Ebola) infection revealed that the host range conferred by Ebo-GP is very broad, extending to cells of a variety of species. Notably, all lymphoid cell lines tested were completely resistant to infection; we speculate that this is due to the absence of a cellular receptor for Ebo-GP on B and T cells. The generation of high-titer MLV(Ebola) pseudotypes will be useful for the analysis of immune responses to Ebola virus infection, development of neutralizing antibodies, analysis of glycoprotein function, and isolation of the cellular receptor(s) for the Ebola virus.
Functional Analysis of the CAAT Box in the Major Late Promoter of the Subgroup C Human Adenoviruses
Authors: Song Byeongwoon , Young C. S. H. 
Published: December 2019

ABSTRACT
Comparisons among sequences predicted to encode the major late promoter (MLP) of adenoviruses from a wide variety of host species show that an inverted CAAT box is among the most highly conserved transcription elements found in the putative MLPs. The high degree of conservation suggests that the CAAT box plays an important role in the function of the MLP in vivo, an idea supported by a previous mutational analysis of the core CCAAT sequence. To address the importance of the CAAT box, in terms both of quantitative levels of transcription and of specificity, a further set of mutations was created and examined in the context of the viral genome. One mutation, CAAT5, contains individual changes at five positions, four of which correspond to invariant residues in a CAAT box consensus derived either by computer analysis or empirically. The CAAT5 mutation had no discernible phenotype by itself but when coupled with the previously described USF0 mutation, which disrupts binding of the upstream stimulating factor (USF) but is otherwise phenotypically silent, gave rise to virus with a severe replication deficiency. Nuclear run-on assays showed that transcription initiation at the mutant MLP was significantly reduced compared with that of the wild type or the virus containing CAAT5 alone. Replication of the double mutant was lower than that of the previously described USF0::CCCAT virus, suggesting that the additional mutations in the CAAT box had further lowered the binding of transcription factor CP1 (also called CBF, NF-Y). Replacement of the CAAT box by an ATF binding site or an OCT1 binding site had no phenotypic effect in an otherwise wild-type background, but replacement in a USF0::CCCAT background led to only partial restoration of the wild-type phenotype. The failure to restore the functional redundancy normally exhibited by the CAAT box and the proximal upstream activating element is consistent with the idea that in the adenovirus MLP the CAAT box is preferred over others as the distal transcriptional element.
Rat Parvovirus Type 1: the Prototype for a New Rodent Parvovirus Serogroup
Authors: Ball-Goodrich Lisa J. , Leland Stuart E. , Johnson Elizabeth A. , Paturzo Frank X. , Jacoby Robert O. 
Published: December 2019

ABSTRACTA newly recognized parvovirus of laboratory rats, designated rat parvovirus type 1a (RPV-1a), was found to be antigenically distinct. It was cloned, sequenced, and compared with the University of Massachusetts strain of rat virus (RV-UMass) and other autonomous parvoviruses. RPV-1a VP1 identity with these viruses never exceeded 69%, thus explaining its antigenic divergence. In addition, RPV-1a had reduced amino acid identity in NS coding regions (82%), reflecting phylogenetic divergence from other rodent parvoviruses. RPV-1a infection in rats had a predilection for endothelium and lymphoid tissues as previously reported for RV. Infectious RPV-1a was isolated 3 weeks after inoculation of infant rats, suggesting that it, like RV, may result in persistent infection. In contrast to RV, RPV-1a was enterotropic, a characteristic previously associated with parvovirus infections of mice rather than rats. RPV-1a also differed from RV in that infection was nonpathogenic for infant rats under conditions where RV infection causes high morbidity and mortality. Thus, RPV-1a is the prototype virus of an antigenically, genetically, and biologically distinct rodent parvovirus serogroup.
Neutralizing Antibodies in Sera from Macaques Infected with Chimeric Simian-Human Immunodeficiency Virus Containing the Envelope Glycoproteins of either a Laboratory-Adapted Variant or a Primary Isolate of Human Immunodeficiency Virus Type 1
Authors: Montefiori David C. , Reimann Keith A. , Wyand Michael S. , Manson Kelledy , Lewis Mark G. , Collman Ronald G. , Sodroski Joseph G. , Bolognesi Dani P. , Letvin Norman L. 
Published: December 2019

ABSTRACTThe magnitude and breadth of neutralizing antibodies raised in response to infection with chimeric simian-human immunodeficiency virus (SHIV) in rhesus macaques were evaluated. Infection with either SHIV-HXB2, SHIV-89.6, or SHIV-89.6PD raised high-titer neutralizing antibodies to the homologous SHIV (SHIV-89.6P in the case of SHIV-89.6PD-infected animals) and significant titers of neutralizing antibodies to human immunodeficiency virus type 1 (HIV-1) strains MN and SF-2. With few exceptions, however, titers of neutralizing antibodies to heterologous SHIV were low or undetectable. The antibodies occasionally neutralized heterologous primary isolates of HIV-1; these antibodies required >40 weeks of infection to reach detectable levels. Notable was the potent neutralization of the HIV-1 89.6 primary isolate by serum samples from SHIV-89.6-infected macaques. These results demonstrate that SHIV-HXB2, SHIV-89.6, and SHIV-89.6P possess highly divergent, strain-specific neutralization epitopes. The results also provide insights into the requirements for raising neutralizing antibodies to primary isolates of HIV-1.
Adenovirus Internalization and Infection Require Dynamin
Authors: Wang Kena , Huang Shuang , Kapoor-Munshi Archana , Nemerow Glen 
Published: December 2019

ABSTRACT
The cell receptors that facilitate adenovirus internalization into cells have been identified; however, the infectious pathway of virus entry has not been established. Adenovirus entry and infection were examined in HeLa cells lacking or overexpressing mutant dynamin, a protein that specifically regulates clathrin-mediated endocytosis. Expression of mutant dynamin significantly reduced adenovirus internalization and gene delivery, indicating a functional requirement for this molecule. These findings are consistent with virus entry via the clathrin-coated pit pathway.
The CAR1 Gene Encoding a Cellular Receptor Specific for Subgroup B and D Avian Leukosis Viruses Maps to the Chicken
tvb
Locus
Authors: Smith Eugene J. , Brojatsch Jürgen , Naughton John , Young John A. T. 
Published: December 2019

ABSTRACT

Host susceptibility to subgroup B, D, and E avian leukosis viruses (ALV) is determined by specific alleles of the chicken
tvb
locus. Recently, a chicken gene that encodes a cellular receptor, designated CAR1, specific for subgroups B and D ALV was cloned, and it was proposed that this gene was the
s3
allele of
tvb
(J. Brojatsch, J. Naughton, M. M. Rolls, K. Zingler, and J. A. T. Young, Cell 87:845–855, 1996). We now report that in a backcross derived from an F
1
(Jungle Fowl × White Leghorn [WL]) male mated with inbred WL females, the cloned ALV receptor gene cosegregated with two markers linked to
tvb
. The two markers used were a

tvb
s1

-specific antigen recognized by the chicken R2 alloantiserum and restriction fragment length polymorphisms associated with the expressed sequence tag com152e. With all three markers, no crossovers were observed among 52 backcross progeny tested and LOD linkage scores of 15.7 were obtained. These data demonstrate that
CAR1
is the subgroup B and D ALV susceptibility gene located at

tvb
s3
.