Induction of apoptosis by sindbis virus occurs at cell entry and does not require virus replication

被引:90
作者
Jan, JT [1 ]
Griffin, DE [1 ]
机构
[1] Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA
关键词
D O I
10.1128/JVI.73.12.10296-10302.1999
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Sindbis virus (SV) is an alphavirus that causes encephalitis in mice and can lead to the apoptotic death of infected cells. To determine the step in virus replication during which apoptosis is triggered, we used UV-inactivated SV, chemicals that block virus fusion or protein synthesis, and cells that do and do not express heparan sulfate, the initial binding molecule for SV infection of many cells. In initial experiments, UV-inactivated neuroadapted SV (NSV) induced apoptosis in Chinese hamster ovary (CHO) cells lacking heparan sulfate in the presence of cycloheximide. When fusion of prebound UV-inactivated NSV was rapidly induced at the plasma membrane by exposure to acidic pH, apoptosis was induced in CHO cells with or without heparan sulfate in the presence or absence of cycloheximide in a virus dose-dependent manner. In N18 neuroblastoma cells, the relative virulence of the virus strain was an important determinant of apoptosis induced by UV-inactivated SV. Treatment of N18 cells with monensin to prevent endosomal acidification an hour before, but not 2 h after, exposure to live NSV blocked the induction of cell death, as did treatment with NH4Cl or bafilomycin A1. These studies indicate that SV can induce apoptosis at the time of fusion with the cell membrane and that virus replication is not required.
引用
收藏
页码:10296 / 10302
页数:7
相关论文
共 50 条
[1]   Noncytopathic Sindbis virus RNA vectors for heterologous gene expression [J].
Agapov, EV ;
Frolov, I ;
Lindenbach, BD ;
Pragai, BM ;
Schlesinger, S ;
Rice, CM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (22) :12989-12994
[2]   NEUROTRANSMITTER SYNTHESIS BY NEUROBLASTOMA CLONES [J].
AMANO, T ;
NIRENBERG, M ;
RICHELSON, E .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1972, 69 (01) :258-+
[3]   BAFILOMYCINS - A CLASS OF INHIBITORS OF MEMBRANE ATPASES FROM MICROORGANISMS, ANIMAL-CELLS, AND PLANT-CELLS [J].
BOWMAN, EJ ;
SIEBERS, A ;
ALTENDORF, K .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (21) :7972-7976
[4]   CAR1, a TNFR-related protein, is a cellular receptor for cytopathic avian leukosis sarcoma viruses and mediates apoptosis [J].
Brojatsch, J ;
Naughton, J ;
Rolls, MM ;
Zingler, K ;
Young, JAT .
CELL, 1996, 87 (05) :845-855
[5]   MEMBRANE-FUSION OF SEMLIKI FOREST VIRUS IN A MODEL SYSTEM - CORRELATION BETWEEN FUSION KINETICS AND STRUCTURAL-CHANGES IN THE ENVELOPE GLYCOPROTEIN [J].
BRON, R ;
WAHLBERG, JM ;
GAROFF, H ;
WILSCHUT, J .
EMBO JOURNAL, 1993, 12 (02) :693-701
[6]   ISOLATION AND CHARACTERIZATION OF CONDITIONAL-LETHAL MUTANTS OF SINDBIS VIRUS [J].
BURGE, BW ;
PFEFFERKORN, ER .
VIROLOGY, 1966, 30 (02) :204-+
[7]   PROGRAMMED KILLING OF HUMAN-CELLS BY MEANS OF AN INDUCIBLE CLONE OF PARVOVIRAL GENES ENCODING NONSTRUCTURAL PROTEINS [J].
CAILLETFAUQUET, P ;
PERROS, M ;
BRANDENBURGER, A ;
SPEGELAERE, P ;
ROMMELAERE, J .
EMBO JOURNAL, 1990, 9 (09) :2989-2995
[8]   Bax-independent inhibition of apoptosis by Bcl-x(L) [J].
Cheng, EHY ;
Levine, B ;
Boise, LH ;
Thompson, CB ;
Hardwick, JM .
NATURE, 1996, 379 (6565) :554-556
[9]   The transmembrane domain in viral fusion: Essential role for a conserved glycine residue in vesicular stomatitis virus G protein [J].
Cleverley, DZ ;
Lenard, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (07) :3425-3430
[10]   A single amino acid change in the E2 glycoprotein of sindbis virus confers neurovirulence by altering an early step of virus replication [J].
Dropulic, LK ;
Hardwick, JM ;
Griffin, DE .
JOURNAL OF VIROLOGY, 1997, 71 (08) :6100-6105