scholarly journals Contribution of Virus-Receptor Interaction to Distinct Viral Proliferation of Neuropathogenic and Nonneuropathogenic Murine Leukemia Viruses in Rat Glial Cells

1999 ◽  
Vol 73 (5) ◽  
pp. 4461-4464 ◽  
Author(s):  
Sayaka Takase-Yoden ◽  
Rihito Watanabe
Keyword(s):  
Leukemia Virus ◽  
Surface Protein ◽  
Receptor Interaction ◽  
Pseudotyped Virus ◽  
Gene Coding ◽  
Order Of Magnitude ◽  
The Difference ◽  
Leukemia Viruses ◽  
Magnitude Difference ◽  
Murine Leukemia

ABSTRACT The efficiency of receptor-mediated entry of pseudotyped virus carrying the surface protein (SU) of clone A8, a neuropathogenic variant of Friend murine leukemia virus (FrMLV), to rat glial cell line F10 was 1 order of magnitude greater than that of pseudotyped virus carrying SU of nonneuropathogenic FrMLV clone 57. Introduction of the gene coding for ecotropic MLV receptor on F10 cells (F10-ecoR) into SIRC cells, which are naturally resistant to FrMLV infection, also revealed the difference in receptor recognition between the A8 and the 57 viruses. Our results show that the difference in receptor utilization between A8-SU and 57-SU only partially explains the 3-order-of-magnitude difference in proliferation between A8 and 57 viruses in F10 cells.

Recent Studies on a Murine Leukemia Virus Grown in Tissue Culture

1967 ◽  
Vol 25 ◽  
pp. 106-107
Author(s):  
L. Z. de Tkaczevski ◽  
E. de Harven ◽  
C. Friend
Keyword(s):  
Tissue Culture ◽  
Solid Tumors ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Supernatant Fluid ◽  
Virus Particles ◽  
Friend Leukemia ◽  
Type C ◽  
Leukemia Viruses ◽  
Murine Leukemia

Despite extensive studies, the correlation between the morphology and pathogenicity of murine leukemia viruses (MLV) has not yet been clarified. The virus particles found in the plasma of leukemic mice belong to 2 distinct groups, 1 or 2% of them being enveloped A particles and the vast majority being of type C. It is generally believed that these 2 types of particles represent different phases in the development of the same virus. Particles of type A have been thought to be an earlier form of type C particles. One of the tissue culture lines established from Friend leukemia solid tumors has provided the material for the present study. The supernatant fluid of the line designated C-1A contains an almost pure population of A particles as illustrated in Figure 1. The ratio is, therefore, the reverse of what is unvariably observed in the plasma of leukemic mice where C particles predominate.

scholarly journals Receptor-Triggered but Alkylation-Arrested Env of Murine Leukemia Virus Reveals the Transmembrane Subunit in a Prehairpin Conformation

2006 ◽  
Vol 80 (19) ◽  
pp. 9921-9925 ◽  
Author(s):  
Michael Wallin ◽  
Maria Ekström ◽  
Henrik Garoff
Keyword(s):  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Surface Protein ◽  
Intermediate Stage ◽  
Central Feature ◽  
Fusion Inhibition ◽  
Mediated Reduction ◽  
Murine Leukemia

ABSTRACT A central feature of the prevailing model for retrovirus fusion is conversion of the transmembrane (TM) subunit from a prehairpin to a hairpin-like structure. The fusion inhibition of many retroviruses, except murine leukemia virus (MLV), with peptides corresponding to interacting regions in the hairpin supports the model. MLV fusion is controlled by isomerization of the intersubunit disulfide in Env. We show here that TM peptides bind to MLV Env that has been arrested at an intermediate stage of activation by alkylation of the isomerization-active thiol in the surface subunit. This inhibits fusion rescue by dithiothreitol-mediated reduction of the surface protein-TM disulfide.

scholarly journals Specificity studies on cytolytic T lymphocytes directed against murine leukemia virus-induced tumors. Analysis of monoclonal cytolytic T lymphocytes.

1982 ◽  
Vol 155 (4) ◽  
pp. 1050-1062 ◽  
Author(s):  
F Plata
Keyword(s):  
T Lymphocytes ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Target Cells ◽  
Cytolytic T Lymphocytes ◽  
Tumor Target ◽  
Induced Tumors ◽  
Definition Of ◽  
Leukemia Viruses ◽  
Murine Leukemia

The specificities of cloned cytolytic T lymphocytes (CTL) were studied for the analysis of CTL populations generated against murine leukemia viruses (MuLV) in H-2 congenic BALB/c (H-2d) and BALB.B (H-2b) mice. In particular, CTL generated in response to tumors induced by Gross MuLV and Friend MuLV were studied; these tumors expressed virus-induced antigens that do not cross-react and that can be distinguished from each other. The systematic study of 92 CTL clones clearly indicated that MuLV-immune CTL were highly heterogeneous with respect to both the intensities of target cell lysis that they mediated and to their specificity of recognition of MuLV-induced tumor target cells. Various categories of CTL clones were identified, ranging from CTL clones tht were tightly H-2 restricted and specific for the immunizing tumor to CTL clones that displayed no discernible patterns of specificity and that attacked a large number of different target cells. In addition, the surface markers of these cloned CTL were defined, and the best conditions for their prolonged maintenance in culture were determined. The present data indicate that future efforts in the definition of target antigens recognized by tumor-specific CTL should be performed with monoclonal lymphocytes.

Generation of infectious Moloney murine leukemia viruses with deletions in the U3 portion of the long terminal repeat

1986 ◽  
Vol 6 (12) ◽  
pp. 4634-4640
Author(s):  
R Hanecak ◽  
S Mittal ◽  
B R Davis ◽  
H Fan
Keyword(s):  
Long Terminal Repeat ◽  
Transient Expression ◽  
Leukemia Virus ◽  
Chloramphenicol Acetyltransferase ◽  
Terminal Repeat ◽  
Tata Box ◽  
Moloney Murine Leukemia Virus ◽  
Chloramphenicol Acetyltransferase Gene ◽  
Leukemia Viruses ◽  
Murine Leukemia

Deletional analysis within the long terminal repeat (LTR) of Moloney murine leukemia virus (M-MuLV) was performed. By molecular cloning, deletions were made in the vicinity of the XbaI site at -150 base pairs (bp) in the U3 region, between the tandemly repeated enhancers and the TATA box. The effects of the deletions on LTR function were measured in two ways. First, deleted LTRs were fused to the bacterial chloramphenicol acetyltransferase gene and used in transient expression assays. Second, infectious M-MuLVs were generated by transfection of M-MuLV proviruses containing the deleted LTRs, and the relative infectivity of the mutant viruses was assessed by XC-syncytial assay. Most of the deleted LTRs examined showed relatively high promoter activity in the transient chloramphenicol acetyltransferase assays, with values ranging from 20 to 50% of the wild-type M-MuLV LTR. Thus, the sequences between the enhancers and the TATA box were not absolutely required for transient expression. However, infectivity of viruses carrying the same deleted LTRs showed more pronounced effects. Deletion of sequences from -195 to -174 bp reduced infectivity 20- to 100-fold. Deletion of sequences within the region from -174 to -122 bp did not affect infectivity, indicating that this region is dispensable. On the other hand, deletion of sequences from -150 to -40 bp reduced infectivity from 5 to 6 logs, although the magnitude of the reduction partly may have reflected threshold envelope protein requirements for positive XC assays. The reduced infectivity did not appear to result from a failure of proviral DNA synthesis or integration by the mutant. Thus, the infectivity measurements identified three functional domains in the region between the enhancers and the TATA box.

scholarly journals Replacement of Murine Leukemia Virus Readthrough Mechanism by Human Immunodeficiency Virus Frameshift Allows Synthesis of Viral Proteins and Virus Replication

2003 ◽  
Vol 77 (5) ◽  
pp. 3345-3350 ◽  
Author(s):  
Marie-Noëlle Brunelle ◽  
Léa Brakier-Gingras ◽  
Guy Lemay
Keyword(s):  
Human Immunodeficiency Virus ◽  
Murine Leukemia Virus ◽  
Stop Codon ◽  
Leukemia Virus ◽  
Viral Proteins ◽  
Immunodeficiency Virus ◽  
Virus Model ◽  
Polyprotein Precursor ◽  
Leukemia Viruses ◽  
Murine Leukemia

ABSTRACT Retroviruses use unusual recoding strategies to synthesize the Gag-Pol polyprotein precursor of viral enzymes. In human immunodeficiency virus, ribosomes translating full-length viral RNA can shift back by 1 nucleotide at a specific site defined by the presence of both a slippery sequence and a downstream stimulatory element made of an extensive secondary structure. This so-called frameshift mechanism could become a target for the development of novel antiviral strategies. A different recoding strategy is used by other retroviruses, such as murine leukemia viruses, to synthesize the Gag-Pol precursor; in this case, a stop codon is suppressed in a readthrough process, again due to the presence of a specific structure adopted by the mRNA. Development of antiframeshift agents will greatly benefit from the availability of a simple animal and virus model. For this purpose, the murine leukemia virus readthrough region was rendered inactive by mutagenesis and the frameshift region of human immunodeficiency virus was inserted to generate a chimeric provirus. This substitution of readthrough by frameshift allows the synthesis of viral proteins, and the chimeric provirus sequence was found to generate infectious viruses. This system could be a most interesting alternative to study ribosomal frameshift in the context of a virus amenable to the use of a simple animal model.

scholarly journals Selection of Optimal Polypurine Tract Region Sequences during Moloney Murine Leukemia Virus Replication

2000 ◽  
Vol 74 (22) ◽  
pp. 10293-10303 ◽  
Author(s):  
Nicole D. Robson ◽  
Alice Telesnitsky
Keyword(s):  
Leukemia Virus ◽  
Moloney Murine Leukemia Virus ◽  
Upstream Sequence ◽  
Wild Type ◽  
The Core ◽  
Polypurine Tract ◽  
Efficient Replication ◽  
Marked Preference ◽  
Leukemia Viruses ◽  
Murine Leukemia

ABSTRACT Retrovirus plus-strand synthesis is primed by a cleavage remnant of the polypurine tract (PPT) region of viral RNA. In this study, we tested replication properties for Moloney murine leukemia viruses with targeted mutations in the PPT and in conserved sequences upstream, as well as for pools of mutants with randomized sequences in these regions. The importance of maintaining some purine residues within the PPT was indicated both by examining the evolution of random PPT pools and from the replication properties of targeted mutants. Although many different PPT sequences could support efficient replication and one mutant that contained two differences in the core PPT was found to replicate as well as the wild type, some sequences in the core PPT clearly conferred advantages over others. Contributions of sequences upstream of the core PPT were examined with deletion mutants. A conserved T-stretch within the upstream sequence was examined in detail and found to be unimportant to helper functions. Evolution of virus pools containing randomized T-stretch sequences demonstrated marked preference for the wild-type sequence in six of its eight positions. These findings demonstrate that maintenance of the T-rich element is more important to viral replication than is maintenance of the core PPT.

scholarly journals Functional Murine Leukemia Virus Vectors Pseudotyped with the Visna Virus Envelope Show Expanded Visna Virus Cell Tropism

2001 ◽  
Vol 75 (23) ◽  
pp. 11464-11473 ◽  
Author(s):  
Linda Bruett ◽  
Janice E. Clements
Keyword(s):  
Murine Leukemia Virus ◽  
Fluorescent Protein ◽  
Leukemia Virus ◽  
Cell Types ◽  
Pseudotyped Virus ◽  
Virus Envelope ◽  
Virus Receptor ◽  
Virus Vectors ◽  
Visna Virus ◽  
Murine Leukemia

ABSTRACT Pseudotype virus vectors serve as a powerful tool for the study of virus receptor usage and entry. We describe the development of murine leukemia virus (MuLV) particles pseudotyped with the visna virus envelope glycoprotein and encoding a green fluorescent protein reporter as a tool to study the expression of the visna virus receptor. Functional MuLV/visna virus pseudotypes were obtained when the cytoplasmic tail of the visna virus envelope TM protein was truncated to 3, 7, or 11 amino acids in length. MuLV/visna virus particles were used to transduce a panel of cell types from various organisms, including sheep, goat, human, hamster, mouse, monkey, and quail. The majority of the cells examined were susceptible to MuLV/visna pseudotype viruses, supporting the notion that the visna virus cellular receptor is a widely expressed protein found in many species. Of 16 different cell types tested, only mouse embryo fibroblast NIH 3T3 cells, hamster ovary CHO cells, and the human promonocyte cell line U937 cells were not susceptible to transduction by the pseudotyped virus. The production of functional MuLV/visna virus pseudotypes has provided a sensitive, biologically relevant system to study visna virus cell entry and envelope-receptor interactions.

scholarly journals Suppression of a Fusion Defect by Second Site Mutations in the Ecotropic Murine Leukemia Virus Surface Protein

1999 ◽  
Vol 73 (6) ◽  
pp. 5034-5042 ◽  
Author(s):  
Tatiana Zavorotinskaya ◽  
Lorraine M. Albritton
Keyword(s):  
Host Cell ◽  
Cell Fusion ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Surface Protein ◽  
Host Cells ◽  
Virus Surface ◽  
Fusion Defect ◽  
Murine Leukemia ◽  
Cell Cell

ABSTRACT Entry of ecotropic murine leukemia virus initiates when the envelope surface protein recognizes and binds to the virus receptor on host cells. The envelope transmembrane protein then mediates fusion of viral and host cell membranes and penetration into the cytoplasm. Using a genetic selection, we isolated an infectious retrovirus variant containing three changes in the surface protein—histidine 8 to arginine, glutamine 227 to arginine, and aspartate 243 to tyrosine. Single replacement of histidine 8 with arginine (H8R) resulted in almost complete loss of infectivity, even though the mutant envelope proteins were stable and efficiently incorporated into virions. Virions carrying H8R envelope were proficient at binding cells expressing receptor but failed to induce cell-cell fusion of XC cells, indicating that the histidine at position 8 plays an essential role in fusion during penetration of the host cell membrane. Thus, there is at least one domain in SU that is involved in fusion; the fusion functions do not reside exclusively in TM. In contrast, envelope with all three changes induced cell-cell fusion of XC cells and produced virions that were 10,000-fold more infectious than those containing only the H8R substitution, indicating that changes at positions 227 and 243 can suppress a fusion defect caused by loss of histidine 8 function. Moreover, the other two changes acted synergistically, indicating that both compensate for the loss of the same essential function of histidine 8. The ability of these changes to suppress this fusion defect might provide a means for overcoming postbinding defects found in targeted retroviral vectors for use in human gene therapy.

scholarly journals Extensive epitranscriptomic methylation of A and C residues on murine leukemia virus transcripts enhances viral gene expression

2019 ◽  
Author(s):  
David G. Courtney ◽  
Andrea Chalem ◽  
Hal P. Bogerd ◽  
Brittany A. Law ◽  
Edward M. Kennedy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Viral Replication ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
Positive Role ◽  
Viral Rnas ◽  
Order Of Magnitude ◽  
Murine Leukemia

AbstractWhile it has been known for several years that viral RNAs are subject to the addition of several distinct covalent modifications to individual nucleotides, collectively referred to as epitranscriptomic modifications, the effect of these editing events on viral gene expression has been controversial. Here, we report the purification of murine leukemia virus (MLV) genomic RNA to homogeneity and show that this viral RNA contains levels ofN6-methyladenosine (m6A), 5-methylcytosine (m5C) and 2’O-methylated (Nm) ribonucleotides that are an order of magnitude higher than detected on bulk cellular mRNAs. Mapping of m6A and m5C residues on MLV transcripts identified multiple discrete editing sites and allowed the construction of MLV variants bearing silent mutations that removed a subset of these sites. Analysis of the replication potential of these mutants revealed a modest but significant attenuation in viral replication in 3T3 cells in culture. Consistent with a positive role for m6A and m5C in viral replication, we also demonstrate that overexpression of the key m6A reader protein YTHDF2 enhances MLV replication, while downregulation of the m5C writer NSUN2 inhibits MLV replication.ImportanceThe data presented in this manuscript demonstrate that MLV RNAs bear an exceptionally high level of the epitranscriptomic modifications m6A, m5C and Nm, thus suggesting that these each facilitate some aspect of the viral replication cycle. Consistent with this hypothesis, we demonstrate that mutational removal of a subset of these m6A or m5C modifications from MLV transcripts inhibits MLV replication incisand a similar result was also observed upon manipulation of the level of expression of key cellular epitranscriptomic cofactors intrans. Together, these results argue that the addition of several different epitranscriptomic modifications to viral transcripts stimulates viral gene expression and suggest that MLV has therefore evolved to maximize the level of these modifications that are added to viral RNAs.

scholarly journals The Entire Nucleotide Sequence of Friend-Related and Paralysis-Inducing PVC-441 Murine Leukemia Virus (MuLV) and Its Comparison with Those of PVC-211 MuLV and Friend MuLV

1998 ◽  
Vol 72 (4) ◽  
pp. 3423-3426 ◽  
Author(s):  
Atsushi Tanaka ◽  
Kiyomasa Oka ◽  
Keiji Tanaka ◽  
Atsushi Jinno ◽  
Sandra K. Ruscetti ◽  
...  
Keyword(s):  
Nucleotide Sequence ◽  
Murine Leukemia Virus ◽  
Chinese Hamster Ovary Cells ◽  
Leukemia Virus ◽  
Chinese Hamster ◽  
Brain Capillary Endothelial Cell ◽  
Ovary Cells ◽  
The Difference ◽  
Entire Nucleotide Sequence ◽  
Murine Leukemia

ABSTRACT PVC-441 murine leukemia virus (MuLV) is a member of the PVC group of Friend MuLV (F-MuLV)-derived neuropathogenic retroviruses. In order to determine the molecular basis for the difference in neuropathogenicity between PVC-441 and the previously characterized PVC-211 MuLVs, the entire nucleotide sequence of PVC-441 MuLV was determined and compared with those of PVC-211 and F-MuLV. The results suggest that PVC-441 and PVC-211 MuLVs were formed as a result of random mutations of F-MuLV and developed differently. The distinct pathogenicities of PVC-441 and PVC-211 MuLVs were maintained in the viruses regenerated from their molecular clones, and the sequences responsible for the pathological differences observed can be localized to the env gene. The amino acid sequence of PVC-441 deduced from its nucleotide sequence revealed a number of differences from PVC-211, the most striking of which was a difference at position 129 of the SU proteins in the two viruses. Host range studies with a brain capillary endothelial cell line (RTEC-6) and Chinese hamster ovary cells (CHO-K1) revealed that PVC-441, like PVC-211, could infect these cells but its efficiency of infection was lower than that of PVC-211. These results may account for the difference in neuropathogenicity between PVC-441 and PVC-211.

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