title: The surface glycoprotein of feline leukemia virus isolate FeLV-945 is a determinant of altered pathogenesis in the presence or absence of the unique viral long terminal repeat.
abstract: Feline leukemia virus (FeLV) is a naturally transmitted gammaretrovirus that infects domestic cats. FeLV-945, the predominant isolate associated with non-T-cell disease in a natural cohort, is a member of FeLV subgroup A but differs in sequence from the FeLV-A prototype, FeLV-A/61E, in the surface glycoprotein (SU) and long terminal repeat (LTR). Substitution of the FeLV-945 LTR into FeLV-A/61E resulted in pathogenesis indistinguishable from that of FeLV-A/61E, namely, thymic lymphoma of T-cell origin. In contrast, substitution of both FeLV-945 LTR and SU into FeLV-A/61E resulted in multicentric lymphoma of non-T-cell origin. These results implicated the FeLV-945 SU as a determinant of pathogenic spectrum. The present study was undertaken to test the hypothesis that FeLV-945 SU can act in the absence of other unique sequence elements of FeLV-945 to determine the disease spectrum. Substitution of FeLV-A/61E SU with that of FeLV-945 altered the clinical presentation and resulted in tumors that demonstrated expression of CD45R in the presence or absence of CD3. Despite the evident expression of CD45R, a typical B-cell marker, T-cell receptor beta (TCRβ) gene rearrangement indicated a T-cell origin. Tumor cells were detectable in bone marrow and blood at earlier times during the disease process, and the predominant SU genes from proviruses integrated in tumor DNA carried markers of genetic recombination. The findings demonstrate that FeLV-945 SU alters pathogenesis, although incompletely, in the absence of FeLV-945 LTR. Evidence demonstrates that FeLV-945 SU and LTR are required together to fully recapitulate the distinctive non-T-cell disease outcome seen in the natural cohort.
authors.affiliation: Department of Microbiology and Immunology and Tulane Cancer Center, Tulane University School of Medicine, New Orleans, Louisiana, USA.
authors.forename: Lisa L
authors.initials: LL
authors.lastname: Bolin
authors.forename: Shamim
authors.initials: S
authors.lastname: Ahmad
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Lobelle-Rich
authors.forename: Tara G
authors.initials: TG
authors.lastname: Ooms
authors.forename: Xavier
authors.initials: X
authors.lastname: Alvarez-Hernandez
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Didier
authors.forename: Laura S
authors.initials: LS
authors.lastname: Levy
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015139:Blotting, Southern; D002415:Cats; D004279:DNA, Viral / Q000235:genetics; D018450:Disease Progression; D005260:Female; D007124:Immunoenzyme Techniques; D005256:Leukemia Virus, Feline / Q000472:pathogenicity* / Q000502:physiology; D008223:Lymphoma / Q000235:genetics / Q000473:pathology* / Q000821:virology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012192:Retroviridae Infections / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D017386:Sequence Homology, Amino Acid; D015996:Survival Rate; D020079:Terminal Repeat Sequences / Q000235:genetics*; D013953:Thymus Neoplasms / Q000235:genetics / Q000473:pathology* / Q000821:virology; D014412:Tumor Virus Infections / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D004279:DNA, Viral; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins
references.citation: Nature. 1984 Mar 8-14;308(5955):149-53
references.pmid: 6199676
references.citation: Scand J Immunol. 1994 May;39(5):419-25
references.pmid: 7514808
references.citation: Nature. 1984 Apr 26-May 2;308(5962):853-6
references.pmid: 6325921
references.citation: Virology. 1993 Oct;196(2):845-8
references.pmid: 8396812
references.citation: Curr Top Microbiol Immunol. 1991;171:67-93
references.pmid: 1667630
references.citation: J Virol. 1992 May;66(5):2885-92
references.pmid: 1313907
references.citation: Retrovirology. 2011 May 13;8:35
references.pmid: 21569491
references.citation: Science. 2001 May 11;292(5519):1106-9
references.pmid: 11352065
references.citation: Oncogene. 2005 Nov 21;24(52):7656-72
references.pmid: 16299527
references.citation: J Gen Virol. 2004 Oct;85(Pt 10):2937-2942
references.pmid: 15448356
references.citation: J Virol. 1994 Apr;68(4):2458-67
references.pmid: 8139030
references.citation: J Exp Med. 2001 Oct 15;194(8):1171-8
references.pmid: 11602645
references.citation: Immunol Rev. 1982;69:5-23
references.pmid: 6984001
references.citation: Science. 1988 Feb 19;239(4842):906-10
references.pmid: 2893454
references.citation: J Virol. 1995 Jun;69(6):3324-32
references.pmid: 7745680
references.citation: J Virol. 2005 Feb;79(3):1351-60
references.pmid: 15650161
references.citation: J Immunol. 1986 Jun 1;136(11):4075-84
references.pmid: 3009614
references.citation: J Virol. 2005 May;79(9):5278-87
references.pmid: 15827142
references.citation: J Virol. 1994 Dec;68(12):8296-303
references.pmid: 7966623
references.citation: Cell. 1982 Dec;31(2 Pt 1):453-63
references.pmid: 6297766
references.citation: J Gen Virol. 1973 Aug;20(2):169-75
references.pmid: 4127732
references.citation: J Immunol. 1997 May 1;158(9):4193-9
references.pmid: 9126980
references.citation: Virus Genes. 1995;11(2-3):147-61
references.pmid: 8828142
references.citation: J Immunol. 2000 May 15;164(10):5221-6
references.pmid: 10799882
references.citation: Virology. 1999 Oct 25;263(2):460-70
references.pmid: 10544118
references.citation: J Immunol. 1992 Oct 1;149(7):2286-94
references.pmid: 1388188
references.citation: Virol J. 2004 Sep 03;1:3
references.pmid: 15507152
references.citation: Microbiol Mol Biol Rev. 2001 Sep;65(3):371-89, table of contents
references.pmid: 11528001
references.citation: Virology. 1995 Dec 20;214(2):431-8
references.pmid: 8553544
references.citation: J Virol. 1990 Jul;64(7):3455-62
references.pmid: 2161948
references.citation: Immunology. 2000 Aug;100(4):417-23
references.pmid: 10929067
references.citation: J Virol. 2000 Jul;74(13):5796-801
references.pmid: 10846058
references.citation: Viruses. 2011 Sep;3(9):1681-98
references.pmid: 21994802
references.citation: J Virol. 1998 Dec;72(12):9955-65
references.pmid: 9811733
references.citation: Cancer Invest. 1992;10(5):371-89
references.pmid: 1327427