A furin-defective cell line is able to process correctly the gp160 of human immunodeficiency virus type 1.
Furin, a subtilisin-like mammalian endoprotease, is thought to be responsible for the processing of many proprotein precursors of cellular and viral origin, including gp160 of human immunodeficiency virus type 1, which share the consensus processing site motif, Arg-X-Lys/Arg-Arg, for protease recognition (for reviews, see P. J. Barr, Cell 66:1-3, 1991, and Y. Nagai, Trends Microbiol. 1:81-87, 1993). To confirm and extend the concept that gp160 is processed by furin, we used here a cell line, LoVo, which was recently demonstrated to be furin defective. Unexpectedly, LoVo cells were found to process gp160 as efficiently as normal cell lines do, hence being able to fuse with CD4-expressing HeLa cells and to produce fully infectious virions. On the other hand, the same cell line was almost totally incapable of processing Newcastle disease virus fusion glycoprotein with a similar oligobasic cleavage recognition motif, providing a strong case for furin-mediated processing. Our present study thus raises a further need to search for and identify the proteinases involved in human immunodeficiency virus type 1 gp160 processing rather than supporting the notion that furin is responsible.
Ohnishi
Y
Y
Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Japan.
Shioda
T
T
Nakayama
K
K
Iwata
S
S
Gotoh
B
B
Hamaguchi
M
M
Nagai
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D016384:Consensus Sequence; D006224:Cricetinae; D045683:Furin; D015686:Gene Products, env / Q000235:genetics / Q000378:metabolism*; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D013381:Subtilisins / Q000235:genetics / Q000378:metabolism*
D015686:Gene Products, env; D019302:HIV Envelope Protein gp160; D011498:Protein Precursors; D013381:Subtilisins; D045683:Furin