A CELL FUSION-INHIBITING MONOCLONAL-ANTIBODY BINDS TO THE PRESUMED STALK DOMAIN OF THE HUMAN PARAINFLUENZA TYPE-2 VIRUS HEMAGGLUTININ-NEURAMINIDASE PROTEIN

被引:24
作者
YUASA, T
KAWANO, M
TABATA, N
NISHIO, M
KUSAGAWA, S
KOMADA, H
MATSUMURA, H
ITO, Y
TSURUDOME, M
机构
[1] MIE UNIV,SCH MED,DEPT MICROBIOL,TSU,MIE 514,JAPAN
[2] SUZUKA UNIV MED SCI & TECHNOL,SUZUKA,MIE 51002,JAPAN
关键词
D O I
10.1006/viro.1995.1035
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Previously, we obtained a neutralizing monoclonal antibody directed against the hemagglutinin-neuraminidase (HN) protein of human parainfluenza type 2 virus (PIV2), which was able to prevent cell fusion without affecting the hemagglutinating and neuraminidase activities. In this study, four escape mutants of PIV2 have been obtained under pressure of the monoclonal antibody. Intriguingly, the HN protein of each mutant proved to have two amino acid substitutions, one of which is at 83Asn or 91Lys, and another one is at 150Leu, 160Ala, or 186Met. One mutant designated F13, which has substitutions at 83Asn and 186Met in the HN protein, could not cause cell fusion in HeLa cells despite its multiple replication, while the other mutants formed typical syncytial cells. The deduced amino acid sequence of F13 fusion (F) protein proved to be identical to that of wild-type F protein, and furthermore, protein expression analyses have revealed that the low-fusion phenotype of F13 was due to its mutated HN protein, whose antigenicity to the monoclonal antibody was abolished by the single mutation at 83Asn. These observations have suggested that the principal epitope for the monoclonal antibody resides in the presumed stalk domain of the HN protein, which may play an important role in promoting cell fusion. (C) 1995 Academic Press, Inc.
引用
收藏
页码:1117 / 1125
页数:9
相关论文
共 30 条
[1]  
AROETI B, 1991, J BIOL CHEM, V266, P15845
[2]   ANTIGENIC AND STRUCTURAL-PROPERTIES OF THE HEMAGGLUTININ-NEURAMINIDASE GLYCOPROTEIN OF HUMAN PARA-INFLUENZA VIRUS TYPE-3 - SEQUENCE-ANALYSIS OF VARIANTS SELECTED WITH MONOCLONAL-ANTIBODIES WHICH INHIBIT INFECTIVITY, HEMAGGLUTINATION, AND NEURAMINIDASE ACTIVITIES [J].
COELINGH, KLV ;
WINTER, CC ;
JORGENSEN, ED ;
MURPHY, BR .
JOURNAL OF VIROLOGY, 1987, 61 (05) :1473-1477
[3]   SEQUENCE AND STRUCTURE ALIGNMENT OF PARAMYXOVIRUS HEMAGGLUTININ-NEURAMINIDASE WITH INFLUENZA-VIRUS NEURAMINIDASE [J].
COLMAN, PM ;
HOYNE, PA ;
LAWRENCE, MC .
JOURNAL OF VIROLOGY, 1993, 67 (06) :2972-2980
[4]   THE FUSION AND HEMAGGLUTININ-NEURAMINIDASE GLYCOPROTEINS OF HUMAN PARAINFLUENZA VIRUS 3 ARE BOTH REQUIRED FOR FUSION [J].
EBATA, SN ;
COTE, MJ ;
KANG, CY ;
DIMOCK, K .
VIROLOGY, 1991, 183 (01) :437-441
[5]   STRUCTURAL FEATURES UNIQUE TO EACH OF THE 3 ANTIGENIC SITES ON THE HEMAGGLUTININ NEURAMINIDASE PROTEIN OF NEWCASTLE-DISEASE VIRUS [J].
GOTOH, B ;
SAKAGUCHI, T ;
NISHIKAWA, K ;
INOCENCIO, NM ;
HAMAGUCHI, M ;
TOYODA, T ;
NAGAI, Y .
VIROLOGY, 1988, 163 (01) :174-182
[6]   PARAMYXOVIRUS MEDIATED CELL-FUSION REQUIRES COEXPRESSION OF BOTH THE FUSION AND HEMAGGLUTININ-NEURAMINIDASE GLYCOPROTEINS [J].
HEMINWAY, BR ;
YU, Y ;
GALINSKI, MS .
VIRUS RESEARCH, 1994, 31 (01) :1-16
[7]   BIOLOGICAL-ACTIVITY OF PARAMYXOVIRUS FUSION PROTEINS - FACTORS INFLUENCING FORMATION OF SYNCYTIA [J].
HORVATH, CM ;
PATERSON, RG ;
SHAUGHNESSY, MA ;
WOOD, R ;
LAMB, RA .
JOURNAL OF VIROLOGY, 1992, 66 (07) :4564-4569
[8]   FUNCTIONAL INTERACTIONS BETWEEN THE FUSION PROTEIN AND HEMAGGLUTININ-NEURAMINIDASE OF HUMAN PARAINFLUENZA VIRUSES [J].
HU, XL ;
RAY, R ;
COMPANS, RW .
JOURNAL OF VIROLOGY, 1992, 66 (03) :1528-1534
[9]   NEUTRALIZATION MAP OF THE HEMAGGLUTININ-NEURAMINIDASE GLYCOPROTEIN OF NEWCASTLE-DISEASE VIRUS - DOMAINS RECOGNIZED BY MONOCLONAL-ANTIBODIES THAT PREVENT RECEPTOR RECOGNITION [J].
IORIO, RM ;
SYDDALL, RJ ;
SHEEHAN, JP ;
BRATT, MA ;
GLICKMAN, RL ;
RIEL, AM .
JOURNAL OF VIROLOGY, 1991, 65 (09) :4999-5006
[10]   INHIBITION OF FUSION BY NEUTRALIZING MONOCLONAL-ANTIBODIES TO THE HEMAGGLUTININ NEURAMINIDASE GLYCOPROTEIN OF NEWCASTLE-DISEASE VIRUS [J].
IORIO, RM ;
GLICKMAN, RL ;
SHEEHAN, JP .
JOURNAL OF GENERAL VIROLOGY, 1992, 73 :1167-1176