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 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 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 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.

scholarly journals Immunoprotective Determinants in Friend Murine Leukemia Virus Envelope Protein

Virology ◽  
1998 ◽  
Vol 248 (1) ◽  
pp. 66-73 ◽  
Author(s):  
Kim J. Hasenkrug ◽  
Diane M. Brooks ◽  
Michael N. Robertson ◽  
R.V. Srinivas ◽  
Bruce Chesebro
Keyword(s):  
Envelope Protein ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Virus Envelope ◽  
Virus Envelope Protein ◽  
Murine Leukemia

scholarly journals Moloney Murine Leukemia Virus Integrase Protein Augments Viral DNA Synthesis in Infected Cells

2001 ◽  
Vol 75 (23) ◽  
pp. 11365-11372 ◽  
Author(s):  
Lilin Lai ◽  
Hongmei Liu ◽  
Xiaoyun Wu ◽  
John C. Kappes
Keyword(s):  
Dna Synthesis ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Specific Interaction ◽  
Proteolytic Processing ◽  
Moloney Murine Leukemia Virus ◽  
Wild Type ◽  
Viral Dna ◽  
Infected Cells ◽  
Murine Leukemia

ABSTRACT Mutations in the IN domain of retroviral DNA may affect multiple steps of the virus life cycle, suggesting that the IN protein may have other functions in addition to its integration function. We previously reported that the human immunodeficiency virus type 1 IN protein is required for efficient viral DNA synthesis and that this function requires specific interaction with other viral components but not enzyme (integration) activity. In this report, we characterized the structure and function of the Moloney murine leukemia virus (MLV) IN protein in viral DNA synthesis. Using an MLV vector containing green fluorescent protein as a sensitive reporter for virus infection, we found that mutations in either the catalytic triad (D184A) or the HHCC motif (H61A) reduced infectivity by approximately 1,000-fold. Mutations that deleted the entire IN (ΔIN) or 34 C-terminal amino acid residues (Δ34) were more severely defective, with infectivity levels consistently reduced by 10,000-fold. Immunoblot analysis indicated that these mutants were similar to wild-type MLV with respect to virion production and proteolytic processing of the Gag and Pol precursor proteins. Using semiquantitative PCR to analyze viral cDNA synthesis in infected cells, we found the Δ34 and ΔIN mutants to be markedly impaired while the D184A and H61A mutants synthesized cDNA at levels similar to the wild type. The DNA synthesis defect was rescued by complementing the Δ34 and ΔIN mutants intrans with either wild-type IN or the D184A mutant IN, provided as a Gag-IN fusion protein. However, the DNA synthesis defect of ΔIN mutant virions could not be complemented with the Δ34 IN mutant. Taken together, these analyses strongly suggested that the MLV IN protein itself is required for efficient viral DNA synthesis and that this function may be conserved among other retroviruses.

Sign in / Sign up

Export Citation Format

Share Document