scholarly journals Functional interaction between the N- and C-terminal domains of murine leukemia virus surface envelope protein

Virology ◽  
2003 ◽  
Vol 310 (1) ◽  
pp. 130-140 ◽  
Author(s):  
Chi-Wei Lu ◽  
Monica J Roth
Keyword(s):  
Envelope Protein ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Functional Interaction ◽  
Virus Surface ◽  
Surface Envelope ◽  
Murine Leukemia ◽  
Terminal Domains

scholarly journals Role of the Mutation Q252R in Activating Membrane Fusion in the Murine Leukemia Virus Surface Envelope Protein

2003 ◽  
Vol 77 (20) ◽  
pp. 10841-10849 ◽  
Author(s):  
Chi-Wei Lu ◽  
Monica J. Roth
Keyword(s):  
Cell Fusion ◽  
Receptor Binding ◽  
Envelope Protein ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Host Cells ◽  
Cell Binding ◽  
Surface Envelope ◽  
Murine Leukemia ◽  
Cell Cell

ABSTRACT Entry of retroviruses into host cells requires the fusion between the viral and cellular membranes. It is unclear how receptor binding induces conformational changes within the surface envelope protein (SU) that activate the fusion machinery residing in the transmembrane envelope protein (TM). In this report, we have isolated a point mutation, Q252R, within the proline-rich region of the 4070A murine leukemia virus SU that altered the virus-cell binding characteristics and induced cell-cell fusion. Q252R displays a SU shedding-sensitive phenotype. Cell-cell fusion is receptor dependent and is observed only in the presence of MuLV Gag-Pol. Both cellular binding and fusion by Q252R are greatly enhanced in conjunction of G100R, a mutation within the SU variable region A which increases viral binding through an independent mechanism. Deletion of a conserved histidine (His36) at the SU N terminus abolished cell-cell fusion by G100R/Q252R Env without compromising virus-cell binding. Although G100R/Q252R virus has no detectable titer, replacement of the N-terminal nine 4070A SU amino acids with the equivalent ecotropic MuLV sequence restored viral infectivity. These studies provide insights into the functional cooperation between multiple elements of SU required to signal receptor binding and activate the fusion machinery.

scholarly journals X-gp70: a third molecular species of the envelope protein gp70 of murine leukemia virus, expressed on mouse lymphoid cells.

1976 ◽  
Vol 143 (4) ◽  
pp. 969-974 ◽  
Author(s):  
J S Tung ◽  
F W Shen ◽  
E Fleissner ◽  
E A Boyse
Keyword(s):  
Molecular Species ◽  
Envelope Protein ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Virus Production ◽  
Lymphoid Cells ◽  
Mouse Strains ◽  
Type Virus ◽  
Murine Leukemia

Three variants of the gp70 envelope component of MuLV are now recognizable serologically: GIX-gp70, 0-gp70, and X-gp70. The last of these, X-gp70, has so far been found only in mice or cells producing abundant C-type virus. This distinguishes X-gp70, provisionally, from the GIX-gp70 and 0-gp70 variants, each of which can be expressed on normal thymocytes without accompanying virus production, as exemplified by mouse strains 129 and B6, respectively. The X-gp70 genotype, however, is not limited to strains of mice-producing abundant virus, because X-gp70+ leukemias occur in strains of mice which do not produce a great deal of virus and whose thymocytes and other tissues are X-gp70-; this is analogous to the appearance of GIX+ leukemias in GIX- mouse strains.

scholarly journals Inhibition of Murine Leukemia Virus Envelope Protein (Env) Processing by Intracellular Expression of the Env N-Terminal Heptad Repeat Region

2005 ◽  
Vol 79 (8) ◽  
pp. 4782-4792 ◽  
Author(s):  
Wu Ou ◽  
Jonathan Silver
Keyword(s):  
Influenza Virus ◽  
Envelope Protein ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Proteolytic Processing ◽  
Structural Motif ◽  
Type I ◽  
Alpha Helices ◽  
Intracellular Expression ◽  
Murine Leukemia

ABSTRACT A conserved structural motif in the envelope proteins of several viruses consists of an N-terminal, alpha-helical, trimerization domain and a C-terminal region that refolds during fusion to bind the N-helix trimer. Interaction between the N and C regions is believed to pull viral and target membranes together in a crucial step during membrane fusion. For several viruses with type I fusion proteins, C regions pack as alpha-helices in the grooves between N-helix monomers, and exogenously added N- and C-region peptides block fusion by inhibiting the formation of the six-helix bundle. For other viruses, including influenza virus and murine leukemia virus (MLV), there is no evidence for comparably extended C-region alpha-helices, although a short, non-alpha-helical interaction structure has been reported for influenza virus. We tested candidate N-helix and C-region peptides from MLV for their ability to inhibit cell fusion but found no inhibitory activity. In contrast, intracellular expression of the MLV N-helix inhibited fusion by efficiently blocking proteolytic processing and intracellular transport of the envelope protein. The results highlight another mechanism by which the N-helix peptides can inhibit fusion.

scholarly journals Host Cell Cathepsins Potentiate Moloney Murine Leukemia Virus Infection

2007 ◽  
Vol 81 (19) ◽  
pp. 10506-10514 ◽  
Author(s):  
Pankaj Kumar ◽  
Deepa Nachagari ◽  
Carolyn Fields ◽  
John Franks ◽  
Lorraine M. Albritton
Keyword(s):  
Envelope Protein ◽  
Murine Leukemia Virus ◽  
Cathepsin B ◽  
Leukemia Virus ◽  
Moloney Murine Leukemia Virus ◽  
Dependent Manner ◽  
Virus Binding ◽  
Dose Dependent ◽  
Murine Leukemia

ABSTRACT The roles of cellular proteases in Moloney murine leukemia virus (MLV) infection were investigated using MLV particles pseudotyped with vesicular stomatitis virus (VSV) G glycoprotein as a control for effects on core MLV particles versus effects specific to Moloney MLV envelope protein (Env). The broad-spectrum inhibitors cathepsin inhibitor III and E-64d gave comparable dose-dependent inhibition of Moloney MLV Env and VSV G pseudotypes, suggesting that the decrease did not involve the envelope protein. Whereas, CA-074 Me gave a biphasic response that differentiated between Moloney MLV Env and VSV G at low concentrations, at which the drug is highly selective for cathepsin B, but was similar for both glycoproteins at higher concentrations, at which CA-074 Me inhibits other cathepsins. Moloney MLV infection was lower on cathepsin B knockout fibroblasts than wild-type cells, whereas VSV G infection was not reduced on the B−/− cells. Taken together, these results support the notion that cathepsin B acts at an envelope-dependent step while another cathepsin acts at an envelope-independent step, such as uncoating or viral-DNA synthesis. Virus binding was not affected by CA-074 Me, whereas syncytium induction was inhibited in a dose-dependent manner, consistent with cathepsin B involvement in membrane fusion. Western blot analysis revealed specific cathepsin B cleavage of SU in vitro, while TM and CA remained intact. Infection could be enhanced by preincubation of Moloney MLV with cathepsin B, consistent with SU cleavage potentiating infection. These data suggested that during infection of NIH 3T3 cells, endocytosis brings Moloney MLV to early lysosomes, where the virus encounters cellular proteases, including cathepsin B, that cleave SU.

In vivo distribution of receptor for ecotropic murine leukemia virus and binding of envelope protein of Friend Murine leukemia virus

2003 ◽  
Vol 148 (6) ◽  
pp. 1175-1184 ◽  
Author(s):  
S. Yamaguchi ◽  
M. Hasegawa ◽  
T. Suzuki ◽  
H. Ikeda ◽  
S. Aizawa ◽  
...  
Keyword(s):  
Envelope Protein ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
In Vivo Distribution ◽  
Murine Leukemia

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 Identification of a Receptor-Binding Pocket on the Envelope Protein of Friend Murine Leukemia Virus

1999 ◽  
Vol 73 (5) ◽  
pp. 3758-3763 ◽  
Author(s):  
Robert A. Davey ◽  
Yi Zuo ◽  
James M. Cunningham
Keyword(s):  
Receptor Binding ◽  
Envelope Protein ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Binding Pocket ◽  
Fusion Pore ◽  
Detectable Effect ◽  
Virus Envelope ◽  
Receptor Binding Site ◽  
Murine Leukemia

ABSTRACT Based on previous structural and functional studies, a potential receptor-binding site composed of residues that form a pocket at one end of the two long antiparallel helices in the receptor-binding domain of Friend 57 murine leukemia virus envelope protein (RBD) has been proposed. To test this hypothesis, directed substitutions for residues in the pocket were introduced and consequences for infection and for receptor binding were measured. Receptor binding was measured initially by a sensitive assay based on coexpression of receptor and RBD inXenopus oocytes, and the findings were confirmed by using purified proteins. Three residues that are critical for both binding and infection (S84, D86, and W102), with side chains that extend into the pocket, were identified. Moreover, when mCAT-1 was overexpressed, the infectivity of Fr57-MLV carrying pocket substitutions was partially restored. Substitutions for 18 adjacent residues and 11 other previously unexamined surface-exposed residues outside of the RBD pocket had no detectable effect on function. Taken together, these findings support a model in which the RBD pocket interacts directly with mCAT-1 (likely residues, Y235 and E237) and multiple receptor-envelope complexes are required to form the fusion pore.

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