scholarly journals Sodium-Dependent myo-Inositol Transporter 1 Is a Cellular Receptor for Mus cervicolor M813 Murine Leukemia Virus

2003 ◽  
Vol 77 (10) ◽  
pp. 5926-5932 ◽  
Author(s):  
Sibyll Hein ◽  
Vladimir Prassolov ◽  
Yuanming Zhang ◽  
Dmitry Ivanov ◽  
Jürgen Löhler ◽  
...  
Keyword(s):  
Host Range ◽  
Conformational Changes ◽  
Murine Leukemia Virus ◽  
Molecular Mechanisms ◽  
Leukemia Virus ◽  
Receptor Gene ◽  
Viral Envelope ◽  
Cell Entry ◽  
Sodium Dependent ◽  
Murine Leukemia

ABSTRACT Retrovirus infection is initiated by binding of the surface (SU) portion of the viral envelope glycoprotein (Env) to specific receptors on cells. This binding triggers conformational changes in the transmembrane portion of Env, leading to membrane fusion and cell entry, and is thus a major determinant of retrovirus tissue and species tropism. The M813 murine leukemia virus (MuLV) is a highly fusogenic gammaretrovirus, isolated from Mus cervicolor, whose host range is limited to mouse cells. To delineate the molecular mechanisms of its restricted host range and its high fusogenic potential, we initiated studies to characterize the cell surface protein that mediates M813 infection. Screening of the T31 mouse-hamster radiation hybrid panel for M813 infectivity localized the receptor gene to the distal end of mouse chromosome 16. Expression of one of the likely candidate genes (slc5a3) within this region in human cells conferred susceptibility to both M813 infection and M813-induced fusogenicity. slc5a3 encodes sodium myo-inositol transporter 1 (SMIT1), thus adding another sodium-dependent transporter to the growing list of proteins used by MuLVs for cell entry. Characterization of SMIT1 orthologues in different species identified several amino acid variations within two extracellular loops that may restrict susceptibility to M813 infection.

scholarly journals Mus cervicolor Murine Leukemia Virus Isolate M813 Belongs to a Unique Receptor Interference Group

2001 ◽  
Vol 75 (10) ◽  
pp. 4490-4498 ◽  
Author(s):  
Vladimir Prassolov ◽  
Sibyll Hein ◽  
Marion Ziegler ◽  
Dmitry Ivanov ◽  
Carsten Münk ◽  
...  
Keyword(s):  
Host Range ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Cell Entry ◽  
Chromosome 2 ◽  
Coding Region ◽  
Common Receptor ◽  
Type C ◽  
Murine Leukemia ◽  
Receptor Interference

ABSTRACT Murine leukemia virus (MuLV) M813 was originally isolated from the Southeast Asian rodent Mus cervicolor. As with the ecotropic MuLVs derived from Mus musculus, its host range is limited to rodent cells. Earlier studies have mapped its receptor to chromosome 2, but it has not been established whether M813 shares a common receptor with any other MuLVs. In this study, we have performed interference assays with M813 and viruses from four interference groups of MuLV. The infection efficiency of M813 was not compromised in cells expressing any one of the other MuLVs, demonstrating that M813 must use a distinct receptor for cell entry. The entire M813 env coding region was molecularly cloned. Sequence analysis revealed high similarity with other MuLVs but with a unique receptor-binding domain. Substitution of M813env sequences in Moloney MuLV resulted in a replication-competent virus with a host range and interference profile similar to those of the biological clone M813. M813 thus defines a novel receptor interference group of type C MuLVs.

scholarly journals Pseudotype Formation of Moloney Murine Leukemia Virus with Sendai Virus Glycoprotein F

1998 ◽  
Vol 72 (6) ◽  
pp. 5296-5302 ◽  
Author(s):  
Martin Spiegel ◽  
Michael Bitzer ◽  
Andrea Schenk ◽  
Heidi Rossmann ◽  
Wolfgang J. Neubert ◽  
...  
Keyword(s):  
Host Range ◽  
Murine Leukemia Virus ◽  
Sendai Virus ◽  
Mdck Cells ◽  
Leukemia Virus ◽  
Direct Proof ◽  
Hepatoma Cells ◽  
The Other ◽  
Moloney Murine Leukemia Virus ◽  
Murine Leukemia

ABSTRACT Mixed infection of cells with both Moloney murine leukemia virus (MoMLV) and related or heterologous viruses produces progeny pseudotype virions bearing the MoMLV genome encapsulated by the envelope of the other virus. In this study, pseudotype formation between MoMLV and the prototype parainfluenza virus Sendai virus (SV) was investigated. We report for the first time that SV infection of MoMLV producer cells results in the formation of MoMLV(SV) pseudotypes, which display a largely extended host range compared to that of MoMLV particles. This could be associated with SV hemagglutinin-neuraminidase (SV-HN) glycoprotein incorporation into MoMLV envelopes. In contrast, solitary incorporation of the other SV glycoprotein, SV fusion protein (SV-F), resulted in a distinct and narrow extension of the MoMLV host range to asialoglycoprotein receptor (ASGP-R)-positive cells (e.g., cultured human hepatoma cells). Since stably ASGP-R cDNA-transfected MDCK cells, but not parental ASGP-R-negative MDCK cells, were found to be transduced by MoMLV(SV-F) pseudotypes and transduction of ASGP-R-expressing cells was found to be inhibited by ASGP-R antiserum, a direct proof for the ASGP-R-restricted tropism of MoMLV(SV-F) pseudotypes was provided. Cultivation of ASGP-R-positive HepG2 hepatoma cells on Transwell-COL membranes led to a significant enhancement of MoMLV(SV-F) titers in subsequent flowthrough transduction experiments, thereby suggesting the importance of ASGP-R accessibility at the basolateral domain for MoMLV(SV-F) pseudotype transduction. The availability of such ASGP-R-restricted MoMLV(SV-F)-pseudotyped vectors opens up new perspectives for future liver-restricted therapeutic gene transfer applications.

Host range conversion of murine leukemia virus resulting from recombination with endogenous virus

1997 ◽  
Vol 142 (1) ◽  
pp. 139-149 ◽  
Author(s):  
A. Kawana ◽  
A. Iwamoto ◽  
T. Odawara ◽  
H. Yoshikura
Keyword(s):  
Host Range ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Endogenous Virus ◽  
Murine Leukemia

scholarly journals Novel Host Range and Cytopathic Variant of Ecotropic Friend Murine Leukemia Virus

2004 ◽  
Vol 78 (22) ◽  
pp. 12189-12197 ◽  
Author(s):  
Yong Tae Jung ◽  
Tiyun Wu ◽  
Christine A. Kozak
Keyword(s):  
Host Range ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Syncytium Formation ◽  
Single Amino Acid ◽  
Receptor Binding Site ◽  
Mus Spicilegus ◽  
Novel Variant ◽  
Novel Host ◽  
Murine Leukemia

ABSTRACT A variant ecotropic Friend murine leukemia virus, F-S MLV, is capable of inducing the formation of large multinucleated syncytia in Mus dunni cells. This cytopathicity resembles that of Spl574 MLV, a novel variant recently isolated from the spleen of a Mus spicilegus mouse neonatally inoculated with Moloney MLV. F-S MLV is an N-tropic Friend MLV that also has the unusual ability to infect hamster cells, which are normally resistant to mouse ecotropic MLVs. Syncytium induction by both F-S MLV and Spl574 is accompanied by the accumulation of large amounts of unintegrated viral DNA, a hallmark of pathogenic retroviruses, but not previously reported for mouse ecotropic gammaretroviruses. Sequencing and site-specific mutagenesis determined that the syncytium-inducing phenotype of F-S MLV can be attributed to a single amino acid substitution (S84A) in the VRA region of the viral env gene. This site corresponds to that of the single substitution previously shown to be responsible for the cytopathicity of Spl574, S82F. The S84A substitution in F-S MLV also contributes to the ability of this virus to infect hamster cells, but Spl574 MLV is unable to infect hamster cells. Because this serine residue is one of the critical amino acids that form the CAT-1 receptor binding site, and because M. dunni and hamster cells have variant CAT-1 receptors, these results suggest that syncytium formation as well as altered host range may be a consequence of altered interaction between virus and receptor.

scholarly journals THE VIRAL ENVELOPE GLYCOPROTEIN OF MURINE LEUKEMIA VIRUS AND THE PATHOGENESIS OF IMMUNE COMPLEX GLOMERULONEPHRITIS OF NEW ZEALAND MICE

1974 ◽  
Vol 140 (4) ◽  
pp. 1011-1027 ◽  
Author(s):  
Takashi Yoshiki ◽  
Robert C. Mellors ◽  
Mette Strand ◽  
J. T. August
Keyword(s):  
New Zealand ◽  
Immune Complex ◽  
Envelope Glycoprotein ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Viral Envelope ◽  
High Concentration ◽  
Immune Complex Glomerulonephritis ◽  
Viral Envelope Glycoprotein ◽  
Murine Leukemia

The use of monospecific antisera for the analysis by radioimmunoassay and immunofluorescence study of two major viral proteins, gp69/71 and p30 of murine leukemia virus, that could be of significance in the pathogenesis of immune complex glomerulonephritis of mice, particularly NZB and B/WF1 hybrid mice, yielded the following conclusions. A remarkably high concentration of viral envelope glycoprotein, gp69/71, was detected in the spleen and serum of New Zealand mice (NZB, NZW, B/WF1, and W/BF1); the concentration in the spleen was 10-fold greater than that found in AKR mice and 30-fold greater than that present in C57BL/6 mice. The gp69/71 was deposited along with bound immunoglobulins, apparently as an immune complex, in the diseased kidneys of mice, and the glomerular site and extent of deposition of gp69/71 was related to the severity of the glomerulonephritis. This study suggests that the pathogenesis of immune complex glomerulonephritis (and vasculitis) in mice is related to the expression of this specific viral envelope glycoprotein and to the host immune response to this protein.

scholarly journals Influence of GlycoGag on the Incorporation of Host Membrane Proteins Into the Envelope of the Moloney Murine Leukemia Virus

2021 ◽  
Vol 1 ◽  
Author(s):  
Mariam Maltseva ◽  
Marc-André Langlois
Keyword(s):  
Murine Leukemia Virus ◽  
Viral Particle ◽  
Leukemia Virus ◽  
Viral Envelope ◽  
Host Protein ◽  
Viral Population ◽  
Phenotypic Characterization ◽  
Particle Level ◽  
Protein Incorporation ◽  
Murine Leukemia

Analysis of viral particle heterogeneity produced from infected cells has been limited by the inefficiency of traditional analytical methods to characterize large populations of viruses at an individual particle level. Flow virometry (FVM) is an emerging technique based on flow cytometry principles that enables a high throughput, multiparametric, and phenotypic characterization of viruses at a single particle resolution. Here, we performed FVM to analyze surface markers found on Murine Leukemia Virus (MLV) and glycosylated Gag-deficient (glycoGag) MLV. The glycoGag viral accessory protein has several roles in the MLV viral infection cycle including directing retroviral assembly and particle release at lipid rafts. Based on previous studies, we hypothesize that glycoGag modulates host protein incorporation into the viral envelope during viral assembly and budding. Here, by using FVM, we reveal that glycoGag is associated with an increased incorporation of the host-derived tetraspanins CD81 and CD63 along with the lipid raft marker and immune antigen Thy1.2 during the assembly and release of viral particles from infected NIH 3T3, EL4, and primary CD4+ T cells. Moreover, we show differences in the uptake of host proteins by viruses that are released from the two cell lines and primary T lymphocytes. Additionally, at the individual viral particle level, we observed a degree of expression heterogeneity of host-derived antigens within the viral population. Finally, certain cellular antigens can show either enrichment or exclusion from the viral envelope depending on whether glycoGag is expressed by the virus. This suggests that glycoGag is involved in a mechanism of selective host protein incorporation into the viral envelope.

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