scholarly journals Retroviral Capsid Determinants of Fv1 NB and NR Tropism

2004 ◽  
Vol 78 (18) ◽  
pp. 9592-9598 ◽  
Author(s):  
Anthony Stevens ◽  
Michael Bock ◽  
Scott Ellis ◽  
Paul LeTissier ◽  
Kate N. Bishop ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Naturally Occurring ◽  
Binding Surface ◽  
Loss Of Susceptibility ◽  
Murine Leukemia ◽  
Specificity Determinants ◽  
Ca Protein

ABSTRACT The specificity determinants for susceptibility to resistance by the Fv1 n and b alleles map to amino acid 110 of the murine leukemia virus CA protein. To study the interaction between Fv1 and CA, we examined changes in CA resulting in the loss of susceptibility to Fv1 resistance in naturally occurring NB- and NR-tropic viruses. A variety of amino acid changes affecting Fv1 tropism were identified, at CA positions 82, 92 to 95, 105, 114, and 117, and they all were mapped to the apparent exterior of virion-associated CA. These amino acids may form a binding surface for Fv1.

scholarly journals The Hypervariable Domain of the Murine Leukemia Virus Surface Protein Tolerates Large Insertions and Deletions, Enabling Development of a Retroviral Particle Display System

1999 ◽  
Vol 73 (3) ◽  
pp. 1802-1808 ◽  
Author(s):  
Samuel C. Kayman ◽  
Han Park ◽  
Maya Saxon ◽  
Abraham Pinter
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Sequence ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Single Chain ◽  
Virus Surface ◽  
Insertions And Deletions ◽  
N Terminus ◽  
Murine Leukemia

ABSTRACT The surface proteins (SU) of murine type-C retroviruses have a central hypervariable domain devoid of cysteine and rich in proline. This 41-amino-acid region of Friend ecotropic murine leukemia virus SU was shown to be highly tolerant of insertions and deletions. Viruses in which either the N-terminal 30 amino acids or the C-terminal 22 amino acids of this region were replaced by the 7-amino-acid sequence ASAVAGA were fully infectious. Insertions of this 7-amino-acid sequence at the N terminus, center, and the C terminus of the hypervariable domain had little effect on envelope protein (Env) function, while this insertion at a position 10 amino acids following the N terminus partially destabilized the association between the SU and transmembrane subunits of Env. Large, complex domains (either a 252-amino-acid single-chain antibody binding domain [scFv] or a 96-amino-acid V1/V2 domain of HIV-1 SU containing eight N-linked glycosylation sites and two disulfides) did not interfere with Env function when inserted in the center or C-terminal portions of the hypervariable domain. The scFv domain inserted into the C-terminal region of the hypervariable domain was shown to mediate binding of antigen to viral particles, demonstrating that it folded into the active conformation and was displayed on the surface of the virion. Both positive and negative enrichment of virions expressing the V1/V2 sequence were achieved by using a monoclonal antibody specific for a conformational epitope presented by the inserted sequence. These results indicated that the hypervariable domain of Friend ecotropic SU does not contain any specific sequence or structure that is essential for Env function and demonstrated that insertions into this domain can be used to extend particle display methodologies to complex protein domains that require expression in eukaryotic cells for glycosylation and proper folding.

scholarly journals Role of Murine Leukemia Virus Reverse Transcriptase Deoxyribonucleoside Triphosphate-Binding Site in Retroviral Replication and In Vivo Fidelity

2000 ◽  
Vol 74 (22) ◽  
pp. 10349-10358 ◽  
Author(s):  
Elias K. Halvas ◽  
Evguenia S. Svarovskaia ◽  
Vinay K. Pathak
Keyword(s):  
Amino Acids ◽  
Viral Replication ◽  
Reverse Transcriptase ◽  
Binding Site ◽  
Reverse Transcription ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Deoxyribonucleoside Triphosphate ◽  
Murine Leukemia

ABSTRACT Retroviral populations exhibit a high evolutionary potential, giving rise to extensive genetic variation. Error-prone DNA synthesis catalyzed by reverse transcriptase (RT) generates variation in retroviral populations. Structural features within RTs are likely to contribute to the high rate of errors that occur during reverse transcription. We sought to determine whether amino acids within murine leukemia virus (MLV) RT that contact the deoxyribonucleoside triphosphate (dNTP) substrate are important for in vivo fidelity of reverse transcription. We utilized the previously described ANGIE P encapsidating cell line, which expresses the amphotropic MLV envelope and a retroviral vector (pGA-1). pGA-1 expresses the bacterial β-galactosidase gene (lacZ), which serves as a reporter of mutations. Extensive mutagenesis was performed on residues likely to interact with the dNTP substrate, and the effects of these mutations on the fidelity of reverse transcription were determined. As expected, most substitution mutations of amino acids that directly interact with the dNTP substrate significantly reduced viral titers (>10,000-fold), indicating that these residues played a critical role in catalysis and viral replication. However, the D153A and A154S substitutions, which are predicted to affect the interactions with the triphosphate, resulted in statistically significant increases in the mutation rate. In addition, the conservative substitution F155W, which may affect interactions with the base and the ribose, increased the mutation rate 2.8-fold. Substitutions of residues in the vicinity of the dNTP-binding site also resulted in statistically significant decreases in fidelity (1.3- to 2.4-fold). These results suggest that mutations of residues that contact the substrate dNTP can affect viral replication as well as alter the fidelity of reverse transcription.

scholarly journals Definition of a 14-Amino-Acid Peptide Essential for the Interaction between the Murine Leukemia Virus Amphotropic Envelope Glycoprotein and Its Receptor

1998 ◽  
Vol 72 (1) ◽  
pp. 428-435 ◽  
Author(s):  
Jean Luc Battini ◽  
Olivier Danos ◽  
Jean Michel Heard
Keyword(s):  
Amino Acid ◽  
Receptor Binding ◽  
Envelope Glycoprotein ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Target Cells ◽  
Structural Constraints ◽  
Binding Interaction ◽  
Receptor Recognition ◽  
Murine Leukemia

ABSTRACT Hydrophilic loops in the receptor binding domain of the amphotropic murine leukemia virus (MLV) envelope glycoprotein (SU) are predicted and may participate in SU-receptor interactions. We have replaced five segments of 6 to 15 amino acids located in each of these regions with an 11-amino-acid tag from the vesicular stomatitis virus glycoprotein (VSV-G). Substitution was compatible with envelope processing, transport, and incorporation into virions. However, three substitution mutants showed a temperature-dependent phenotype, suggesting structural unstability. Accessibility of the tagging epitope for a monoclonal anti-VSV-G antibody was greater in oligomeric than in monomeric SUs when insertion was done in VRA, a domain essential for receptor recognition. In contrast, accessibility was independent of structural constraints when insertion was done in VRB, a domain playing an accessory role in receptor binding. Interaction with the amphotropic receptor was investigated by interference assay and study of binding and infection of target cells with MLV particles coated with the substituted envelopes. Envelope-receptor interaction was abolished when substitution was performed in a potential loop-forming segment located at the N-terminal half of VRA. Although interaction was affected to variable extents, depending on the substituted segment, other mutants conserved the ability to interact with the amphotropic receptor. These experiments indicate the 14-amino-acid segment between positions 50 and 64 of SU as an essential determinant of amphotropic-receptor recognition. They also show that a foreign linear epitope can be tolerated in several locations of the amphotropic SU receptor binding site, and this result has implications for the design of targeted retroviral vectors.

scholarly journals A MAJOR GENETIC LOCUS AFFECTING RESISTANCE TO INFECTION WITH MURINE LEUKEMIA VIRUSES

1973 ◽  
Vol 137 (3) ◽  
pp. 850-853 ◽  
Author(s):  
Wallace P. Rowe ◽  
James B. Humphrey ◽  
Frank Lilly
Keyword(s):  
Murine Leukemia Virus ◽  
Genetic Locus ◽  
Leukemia Virus ◽  
Chromosome 4 ◽  
Group Viii ◽  
Naturally Occurring ◽  
Mouse Cells ◽  
Resistance To Infection ◽  
Leukemia Viruses ◽  
Murine Leukemia

The Fv-1 gene, which regulates sensitivity of mouse cells to infection by naturally occurring host-range types of murine leukemia virus, was shown to be located on linkage group VIII (chromosome 4), 39 map units from b.

scholarly journals A Single Amino Acid Change in the Murine Leukemia Virus Capsid Gene Responsible for theFv1nr Phenotype

2000 ◽  
Vol 74 (11) ◽  
pp. 5385-5387 ◽  
Author(s):  
Yong Tae Jung ◽  
Christine A. Kozak
Keyword(s):  
Amino Acid ◽  
Murine Leukemia Virus ◽  
Amino Acid Change ◽  
Leukemia Virus ◽  
Single Amino Acid ◽  
Amino Acid Difference ◽  
Site Specific ◽  
Single Amino Acid Change ◽  
Leukemia Viruses ◽  
Murine Leukemia

ABSTRACT The nr allele at the mouse Fv1 restriction locus governs resistance to B-tropic and some N-tropic murine leukemia viruses (MLVs). Sequence analysis and site-specific mutagenesis of N-tropic MLVs identified a single amino acid difference responsible for this restriction that is distinct from the site that governs N or B tropism. Viruses with other substitutions at this site were evaluated for altered replication patterns.

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