Paramyxovirus-induced syncytium cell formation is suppressed by a dominant negative fusion regulatory protein-1 (FRP-1)/CD98 mutated construct: an important role of FRP-1 in virus-induced cell fusion.
Syncytium formation and subsequent generalized cell fusion have been reported as potentially important mechanisms of virus-induced cytotoxic effects. We tried to clarify the roles of fusion regulatory factor-1 (FRP-1) in virus-induced cell fusion. Two mutated human FRP-1/CD98 proteins [FRP-1/HN, in which the cytoplasmic domain was replaced with the cytoplasmic domain of human parainfluenza virus type 2 (HPIV-2) haemagglutinin-neuraminidase (HN), and FRP-1/330 (serine), in which a cysteine at amino acid 330 was mutated to serine], when expressed stably in L929 cells, were lacking in cell-fusion-enhancing activity stimulated by anti-FRP-1 antibodies. Anti-FRP-1 antibodies enhanced Newcastle disease virus (NDV)-mediated polykaryocyte formation in parent HeLa cells, while anti-FRP-1 antibodies showed no/low effect on polykaryocyte formation in NDV-infected HeLa cells constitutively expressing FRP-1/HN (HeLa-FRP-1/HN cells), indicating that the FRP-1/HN molecule is capable of acting as a dominant negative inhibitor. Furthermore, when HeLa-FRP-1/HN cells were infected with various rubulaviruses (HPIV-2, mumps virus, simian viruses 5 and 41), virus-induced cell fusion was also suppressed, although virus replication was not inhibited in these cells, showing that FRP-1 molecules are required for virus-induced cell fusion. Therefore, FRP-1 is considered to be related to the pathogenesis of paramyxoviruses.
Okamoto
K
K
Department of Microbiology, Mie University School of Medicine, Japan.
Ohgimoto
S
S
Nishio
M
M
Tsurudome
M
M
Kawano
M
M
Komada
H
H
Ito
M
M
Sakakura
Y
Y
Ito
Y
Y
D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002459:Cell Fusion; D002522:Chlorocebus aethiops; D027261:Fusion Regulatory Protein-1; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D018108:Respirovirus; D010253:Respirovirus Infections / Q000473:pathology / Q000821:virology*; D014709:Vero Cells
D015703:Antigens, CD; D002352:Carrier Proteins; D027261:Fusion Regulatory Protein-1