title: Feline leukemia virus infection requires a post-receptor binding envelope-dependent cellular component.
abstract: Gammaretrovirus receptors have been suggested to contain the necessary determinants to mediate virus binding and entry. Here, we show that murine NIH 3T3 and baby hamster kidney (BHK) cells overexpressing receptors for subgroup A, B, and C feline leukemia viruses (FeLVs) are weakly susceptible (10(1) to 10(2) CFU/ml) to FeLV pseudotype viruses containing murine leukemia virus (MLV) core (Gag-Pol) proteins, whereas FeLV receptor-expressing murine Mus dunni tail fibroblast (MDTF) cells are highly susceptible (10(4) to 10(6) CFU/ml). However, NIH 3T3 cells expressing the FeLV subgroup B receptor PiT1 are highly susceptible to gibbon ape leukemia virus pseudotype virus, which differs from the FeLV pseudotype viruses only in the envelope protein. FeLV resistance is not caused by a defect in envelope binding, low receptor expression levels, or N-linked glycosylation. Resistance is not alleviated by substitution of the MLV core in the FeLV pseudotype virus with FeLV core proteins. Interestingly, FeLV resistance is alleviated by fusion of receptor-expressing NIH 3T3 and BHK cells with MDTF or human TE671 cells, suggesting the absence of an additional cellular component in NIH 3T3 and BHK cells that is required for FeLV infection. The putative FeLV-specific cellular component is not a secreted factor, as MDTF conditioned medium does not alleviate the block to FeLV infection. Together, our findings suggest that FeLV infection requires an additional envelope-dependent cellular component that is absent in NIH 3T3 and BHK cells but that is present in MDTF and TE671 cells.
authors.affiliation: The Hospital for Sick Children, Cell Biology Program, 555 University Avenue, Toronto, ON M5G 1X8, Canada.
authors.forename: Naveen
authors.initials: N
authors.lastname: Hussain
authors.forename: Kelly R
authors.initials: KR
authors.lastname: Thickett
authors.forename: Hong
authors.initials: H
authors.lastname: Na
authors.forename: Cherry
authors.initials: C
authors.lastname: Leung
authors.forename: Chetankumar S
authors.initials: CS
authors.lastname: Tailor
mesh_terms: D000818:Animals; D002415:Cats; D002478:Cells, Cultured; D006224:Cricetinae; D005434:Flow Cytometry; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism / Q000821:virology; D005256:Leukemia Virus, Feline / Q000472:pathogenicity*; D016582:Leukemia, Feline / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D008565:Membrane Proteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D011485:Protein Binding; D011991:Receptors, Virus / Q000378:metabolism*; D050817:Transcription Factor Pit-1 / Q000378:metabolism; D014758:Viral Core Proteins / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000378:metabolism*; D014771:Virion / Q000502:physiology; D053585:Virus Attachment
chemical_list: C492690:FLVCR1 protein, human; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C494187:POU1F1 protein, human; D011991:Receptors, Virus; C492292:Slc19a2 protein, mouse; D050817:Transcription Factor Pit-1; D014758:Viral Core Proteins; D014759:Viral Envelope Proteins; C074548:feline leukemia virus receptor