Abnormal processing of a recombinant feline leukemia virus envelope polyprotein and its interference with subgroup C virus infection.
Processing of the env polyprotein of a noninfectious feline leukemia virus (FeLV) recombinant, named r6gp, was examined in human-transfected cells. The r6gp provirus was previously generated in the frame of FeLV, subgroup B, GA clone with substitution of all but 40 C-terminal amino acid sequences of the surface glycoprotein (SU) from an endogenous FeLV provirus element (CFE-6). Although r6gp produced a normal size (85 kDa) env glycoprotein precursor, the product, unlike the precursor of the parental virus, was neither additionally glycosylated nor further processed into mature env proteins. Biochemical observations were consistent with the idea that the chimeric env polyprotein was trapped in the endoplasmic reticulum (ER) and were directly supported by immunofluorescence microscopy analyses. Interestingly, the residence of the chimeric protein in the ER specifically interfered with FeLV, subgroup C (Sarma) virus infection but not the parental FeLV-B virus infection. Since FeLV-C provirus sequences could be readily detected in the infected cells, it appeared that r6gp env expression did not block entry of the challenge virus. While FeLV-B and CFE-6 env genes share an extensive overall sequence homology, a variable region (region VI) of CFE-6 near the C-terminus of SU, which was retained in the r6gp construct, exhibits a considerably higher degree of homology to FeLV-C than FeLV-B. Thus, we propose that region VI is involved in conferring specificity for the env polyprotein oligomerization in the ER, and that co-oligomerization of the trapped r6gp env with FeLV-C is the reason for specific interference with FeLV-C infection. The results also demonstrate for the first time a functional abnormality of a recombinant FeLV env gene which is structurally similar to those commonly detected in FeLV-induced feline lymphosarcomas.
Bechtel
M K
MK
Department of Biochemistry and Molecular Biology, University of Southern California School of Medicine, Los Angeles 90033.
Stallcup
M R
MR
Bedgood
R M
RM
Corey
J L
JL
Pandey
R
R
Roy-Burman
P
P
D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D004279:DNA, Viral; D005455:Fluorescent Antibody Technique; D006801:Humans; D007700:Kinetics; D005256:Leukemia Virus, Feline / Q000378:metabolism* / Q000502:physiology; D008969:Molecular Sequence Data; D009154:Mutation; D011499:Protein Processing, Post-Translational; D016865:Reassortant Viruses; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*; D014762:Viral Interference
D004279:DNA, Viral; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins