Previous Article | Next Article 
J Virol, April 1998, p. 3018-3028, Vol. 72, No. 4
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Human Parvovirus B19 Nonstructural (NS1) Protein
Induces Apoptosis in Erythroid Lineage Cells
Stanley
Moffatt,
Nobuo
Yaegashi,
Kohtaro
Tada,
Nobuyuki
Tanaka, and
Kazuo
Sugamura*
Department of Microbiology and Immunology,
Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku,
Sendai 980-77, Japan
Received 29 September 1997/Accepted 19 December 1997
Infection of erythroid-lineage cells by human parvovirus B19 is
characterized by a gradual cytocidal effect. Accumulating evidence now
implicates the nonstructural (NS1) protein of the virus in
cytotoxicity, but the mechanism underlying the NS1-induced cell death
is not known. Using a stringent regulatory system, we demonstrate
that NS1 cytotoxicity is closely related to apoptosis, as evidenced by
cell morphology, genomic DNA fragmentation, and cell cycle analysis
with the human erythroleukemia cell line K562 and the
erythropoietin-dependent megakaryocytic cell line UT-7/Epo. Apoptosis
was significantly inhibited by an interleukin-1
(IL-1
)-converting enzyme (ICE)/CED-3 family protease inhibitor,
Ac-DEVD-CHO (CPP32; caspase 3), whereas a similar
inhibitor of ICE (caspase 1), Ac-YVAD-CHO, had no effect. Furthermore,
stable expression of the human Bcl-2 proto-oncogene resulted in
near-total protection from cell death in response to NS1 induction.
Mutations engineered into the nucleoside triphosphate-binding domain of
NS1 significantly rescued cells from NS1-induced apoptosis without
having any effect on NS1-induced activation of the IL-6 gene expression
which is mediated by NF-
B. Furthermore, using pentoxifylline, an
inhibitor of NF-
B activation, we demonstrate that the
NF-
B-mediated IL-6 activation by NS1 is uncoupled from the apoptotic
pathway. This functional dissection indicates a complexity underlying
the biochemical function of human parvovirus NS1 in transcriptional
activation and induction of apoptosis. Our findings indicate that NS1
of parvovirus B19 induces cell death by apoptosis in at least
erythroid-lineage cells by a pathway that involves caspase 3, whose
activation may be a key event during NS1-induced cell death.
*
Corresponding author. Mailing address: Department of
Microbiology and Immunology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-77, Japan. Phone: 81-22-717-8096. Fax: 81-22-273-2787. E-mail:
sugamura{at}mail.cc.tohoku.ac.jp.
This article has been cited by other articles:
-
Suzuki, M., Yoto, Y., Ishikawa, A., Tsutsumi, H.
(2009). Analysis of Nucleotide Sequences of Human Parvovirus B19 Genome Reveals Two Different Modes of Evolution, a Gradual Alteration and a Sudden Replacement: a Retrospective Study in Sapporo, Japan, from 1980 to 2008. J. Virol.
83: 10975-10980
[Abstract]
[Full Text]
-
Guan, W., Cheng, F., Yoto, Y., Kleiboeker, S., Wong, S., Zhi, N., Pintel, D. J., Qiu, J.
(2008). Block to the Production of Full-Length B19 Virus Transcripts by Internal Polyadenylation Is Overcome by Replication of the Viral Genome. J. Virol.
82: 9951-9963
[Abstract]
[Full Text]
-
Duechting, A., Tschope, C., Kaiser, H., Lamkemeyer, T., Tanaka, N., Aberle, S., Lang, F., Torresi, J., Kandolf, R., Bock, C.-T.
(2008). Human Parvovirus B19 NS1 Protein Modulates Inflammatory Signaling by Activation of STAT3/PIAS3 in Human Endothelial Cells. J. Virol.
82: 7942-7952
[Abstract]
[Full Text]
-
Ekman, A., Hokynar, K., Kakkola, L., Kantola, K., Hedman, L., Bonden, H., Gessner, M., Aberham, C., Norja, P., Miettinen, S., Hedman, K., Soderlund-Venermo, M.
(2007). Biological and Immunological Relations among Human Parvovirus B19 Genotypes 1 to 3. J. Virol.
81: 6927-6935
[Abstract]
[Full Text]
-
Waldman, M., Kopp, J. B.
(2007). Parvovirus B19 and the Kidney. CJASN
2: S47-S56
[Abstract]
[Full Text]
-
Lupescu, A., Bock, C.-T., Lang, P. A., Aberle, S., Kaiser, H., Kandolf, R., Lang, F.
(2006). Phospholipase A2 Activity-Dependent Stimulation of Ca2+ Entry by Human Parvovirus B19 Capsid Protein VP1. J. Virol.
80: 11370-11380
[Abstract]
[Full Text]
-
Abdel-Latif, L., Murray, B. K., Renberg, R. L., O'Neill, K. L., Porter, H., Jensen, J. B., Johnson, F. B.
(2006). Cell death in bovine parvovirus-infected embryonic bovine tracheal cells is mediated by necrosis rather than apoptosis. J. Gen. Virol.
87: 2539-2548
[Abstract]
[Full Text]
-
Zhi, N., Mills, I. P., Lu, J., Wong, S., Filippone, C., Brown, K. E.
(2006). Molecular and Functional Analyses of a Human Parvovirus B19 Infectious Clone Demonstrates Essential Roles for NS1, VP1, and the 11-Kilodalton Protein in Virus Replication and Infectivity.. J. Virol.
80: 5941-5950
[Abstract]
[Full Text]
-
Thorpe, R., Swanson, S. J
(2005). Current Methods for Detecting Antibodies against Erythropoietin and Other Recombinant Proteins. CVI
12: 28-39
[Full Text]
-
Poole, B. D., Karetnyi, Y. V., Naides, S. J.
(2004). Parvovirus B19-Induced Apoptosis of Hepatocytes. J. Virol.
78: 7775-7783
[Abstract]
[Full Text]
-
Young, N. S., Brown, K. E.
(2004). Parvovirus B19. NEJM
350: 586-597
[Full Text]
-
Segovia, J. C., Guenechea, G., Gallego, J. M., Almendral, J. M., Bueren, J. A.
(2003). Parvovirus Infection Suppresses Long-Term Repopulating Hematopoietic Stem Cells. J. Virol.
77: 8495-8503
[Abstract]
[Full Text]
-
Best, S. M., Shelton, J. F., Pompey, J. M., Wolfinbarger, J. B., Bloom, M. E.
(2003). Caspase Cleavage of the Nonstructural Protein NS1 Mediates Replication of Aleutian Mink Disease Parvovirus. J. Virol.
77: 5305-5312
[Abstract]
[Full Text]
-
Morita, E., Nakashima, A., Asao, H., Sato, H., Sugamura, K.
(2003). Human Parvovirus B19 Nonstructural Protein (NS1) Induces Cell Cycle Arrest at G1 Phase. J. Virol.
77: 2915-2921
[Abstract]
[Full Text]
-
Labrada, L., Bodelon, G., Vinuela, J., Benavente, J.
(2002). Avian Reoviruses Cause Apoptosis in Cultured Cells: Viral Uncoating, but Not Viral Gene Expression, Is Required for Apoptosis Induction. J. Virol.
76: 7932-7941
[Abstract]
[Full Text]
-
Heegaard, E. D., Brown, K. E.
(2002). Human Parvovirus B19. Clin. Microbiol. Rev.
15: 485-505
[Abstract]
[Full Text]
-
Fu, Y., Ishii, K. K., Munakata, Y., Saitoh, T., Kaku, M., Sasaki, T.
(2002). Regulation of Tumor Necrosis Factor Alpha Promoter by Human Parvovirus B19 NS1 through Activation of AP-1 and AP-2. J. Virol.
76: 5395-5403
[Abstract]
[Full Text]
-
Chisaka, H., Morita, E., Murata, K., Ishii, N., Yaegashi, N., Okamura, K., Sugamura, K.
(2002). A transgenic mouse model for non-immune hydrops fetalis induced by the NS1 gene of human parvovirus B19. J. Gen. Virol.
83: 273-281
[Abstract]
[Full Text]
-
Kerr, J. R., Barah, F., Mattey, D. L., Laing, I., Hopkins, S. J., Hutchinson, I. V., Tyrrell, D. A. J.
(2001). Circulating tumour necrosis factor-{alpha} and interferon-{gamma} are detectable during acute and convalescent parvovirus B19 infection and are associated with prolonged and chronic fatigue. J. Gen. Virol.
82: 3011-3019
[Abstract]
[Full Text]
-
Morita, E., Tada, K., Chisaka, H., Asao, H., Sato, H., Yaegashi, N., Sugamura, K.
(2001). Human Parvovirus B19 Induces Cell Cycle Arrest at G2 Phase with Accumulation of Mitotic Cyclins. J. Virol.
75: 7555-7563
[Abstract]
[Full Text]
-
MITCHELL, L. A., LEONG, R., ROSENKE, K. A.
(2001). Lymphocyte recognition of human parvovirus B19 non-structural (NS1) protein: associations with occurrence of acute and chronic arthropathy?. J Med Microbiol
50: 627-635
[Abstract]
[Full Text]
-
Ueno, Y., Harada, T., Iseki, H., Ohshima, T., Sugiyama, F., Yagami, K.-i.
(2001). Propagation of Rat Parvovirus in Thymic Lymphoma Cell Line C58(NT)D and Subsequent Appearance of a Resistant Cell Clone after Lytic Infection. J. Virol.
75: 3965-3970
[Abstract]
[Full Text]
-
Jordan, J. A., Huff, D., DeLoia, J. A.
(2001). Placental Cellular Immune Response in Women Infected with Human Parvovirus B19 during Pregnancy. CVI
8: 288-292
[Abstract]
[Full Text]
-
Meeus, G., Messiaen, T., Verhoef, G., Vanrenterghem, Y.
(2000). New-onset anaemia following kidney transplantation. Nephrol Dial Transplant
15: 2059-2061
[Full Text]
-
Schmidt, M., Afione, S., Kotin, R. M.
(2000). Adeno-Associated Virus Type 2 Rep78 Induces Apoptosis through Caspase Activation Independently of p53. J. Virol.
74: 9441-9450
[Abstract]
[Full Text]
-
Kerr, J. R
(2000). Pathogenesis of human parvovirus B19 in rheumatic disease. Ann Rheum Dis
59: 672-683
[Full Text]
-
Sol, N., Le Junter, J., Vassias, I., Freyssinier, J. M., Thomas, A., Prigent, A. F., Rudkin, B. B., Fichelson, S., Morinet, F.
(1999). Possible Interactions between the NS-1 Protein and Tumor Necrosis Factor Alpha Pathways in Erythroid Cell Apoptosis Induced by Human Parvovirus B19. J. Virol.
73: 8762-8770
[Abstract]
[Full Text]
-
Segovia, J. C., Gallego, J. M., Bueren, J. A., Almendral, J. M.
(1999). Severe Leukopenia and Dysregulated Erythropoiesis in SCID Mice Persistently Infected with the Parvovirus Minute Virus of Mice. J. Virol.
73: 1774-1784
[Abstract]
[Full Text]