Retrovirus isolated from mantle histiocytes in mantle cell lymphoma
AssigneeThe Regents of the University of California
InventorsMicahael S. McGrath, Brian Herndier
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Abstract
The present invention features an isolated, intact virus associated with human lymphoma, and originally isolated from a mantle cell lymphoma, referred to herein as a mantle histiocyte retrovirus (MHRV). The invention also features compositions and methods for detecting MHRV, as well as methods and compositions for propagating MHRV in vitro, screening for anti-MHRV agents, and generation of attenuated MHRV strains.
Claims58
An isolated mantle histiocyte retrovirus (MHRV) particle.
An isolated MHRV particle wherein the particle:
- is isolatable from a human lymphoma;
- has a particle diameter of from about 90 nm to 110 nm;
- has a membrane lipid bilayer;
- has an RNA genome visible by electron microscopy as a conical eccentric nucleoid;
- and
- has a GAG envelope polypeptide comprising amino acid residues 1-22 of the amino acid sequence of SEQ ID NO:8.
An isolated MHRV particle wherein the particle:
- is isolatable from a human lymphoma;
- has a particle diameter of from about 90 nm to 110 nm;
- has a membrane lipid bilayer;
- and
- has an RNA genome visible by electron microscopy as a conical eccentric nucleoid;
- and
- wherein the RNA genome comprises a nucleic acid sequence corresponding to nucleotide residues 1-66 of SEQ ID NO:7 or a complement thereof.
An isolated polynucleotide comprising a sequence encoding a polypeptide comprising an amino acid sequence of at least 4 contiguous amino acid residues of amino acid residues 1-22 of SEQ ID NO:8.
An isolated polynucleotide comprising a sequence of at least 12 contiguous residues of nucleic acid residues 1-66 of SEQ ID NO:7 or a complement thereof.
An isolated polynucleotide comprising a sequence that hybridizes under conditions of high stringency to the polynucleotide sequence of nucleotides 1-66 of SEQ ID NO:
- or a complement thereof 7.
An isolated polynucleotide comprising a sequence having at least 65% identity to at least 12 contiguous nucleotides of nucleic acid residues 1-66 of SEQ ID NO:7 or a complement thereof.
An isolated MHRV GAG polypeptide.
A method for detecting mantle histiocyte retrovirus (MHRV) in a sample, the method comprising:
- contacting a biological sample suspected of containing MHRV with an MHRV-specific probe, said contacting being for a time sufficient for binding of the MHRV-specific probe to the sample to form complexes between the probe and a probe target;
- and
- detecting the presence or absence of complexes of the MHRV-specific probe and the probe target in the sample;
- wherein detection of complexes in the sample indicates MHRV is present in the sample.
A method for detecting a mantle histiocyte retrovirus (MHRV) in a sample, the method comprising:
- contacting a biological sample suspected of containing MHRV with a first MHRV-specific nucleic acid probe and with a second MHRV-specific nucleic acid probe, wherein the first probe and the second probe each comprise at least 15 contiguous nucleotides of a nucleic acid sequence of SEQ ID NO:7 or a complement thereof, said contacting being under conditions effective to produce an amplified DNA product;
- and
- detecting the presence or absence amplified DNA product;
- wherein detection of amplified DNA product corresponding to an amplified DNA product expected from a nucleic acid sequence comprising SEQ ID NO:7 or a complement thereof indicates the MHRV is present in the sample.
A kit for detection of mantle histiocyte retrovirus (MHRV), the kit comprising an MHRV-specific probe, wherein the probe is:
- an MHRV-specific nucleic acid probe that specifically hybridizes to a sequence encoding an MHRV GAG polypeptide;
- an MHRV-specific GAG antibody;
- or
- an MHRV polypeptide that specifically binds an anti-MHRV GAG antibody.
A method of screening for anti-MHRV antiviral agents, the method comprising:
- contacting a candidate agent with a culture comprising a mammalian cell infected with MHRV, which cell produces viral particles;
- and
- detecting MHRV viral particles in supernatant of the culture;
- wherein a decrease in MHRV viral particles in the supernatant indicates that the candidate agent as activity as an anti-MHRV antiviral agent.
A method for detecting an MHRV-associated disease, the method comprising:
- contacting a biological sample with an MHRV-specific probe, wherein the biological sample was obtained from a subject suspected of having an MHRV-associated disease, said contacting being for a time sufficient for binding of the MHRV-specific probe to the sample to form complexes between the probe and a probe target;
- and
- detecting complexes of the MHRV-specific probe and the probe target in the sample;
- wherein detection of complexes in the sample indicates MHRV is present in the sample, which indicates the subject may have an MHRV-associated disease.
An immunogenic composition comprising an immunogenic polypeptide, wherein the immunogenic polypeptide comprises an amino acid sequence of amino acid residues 1-22 of a GAG polypeptide of mantle histiocyte retrovirus (MHRV).
An immunogenic composition comprising a nucleic acid molecule having a sequence encoding an immunogenic polypeptide, wherein the immunogenic polypeptide comprises an amino acid sequence of amino acid residues 1-22 of a GAG polypeptide of mantle histiocyte retrovirus (MHRV), and wherein the nucleic acid sequence is adapted for expression in a mammalian cell.
Dependencies are inferred from the claim text.