Restriction of vaccinia virus replication by a ced-3 and ced-4-dependent pathway in Caenorhabditiselegans
- Wan-Hsin Liu*,
- Yi-Ling Lin†,
- Jia-Pey Wang‡,
- Willisa Liou§,
- Roger F. Hou*,
- Yi-Chun Wu¶,‖, and
- Ching-Len Liao‡,‖
- *Department of Entomology, National Chung Hsing University, Taichung, Taiwan 40227, Republic of China;
- †Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan 115, Republic of China;
- ‡Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan 114, Republic of China;
- §Department of Anatomy, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan 333, Republic of China; and
- ¶Institute of Molecular and Cellular Biology and Department of Life Science, National Taiwan University, Taipei, Taiwan 106, Republic of China
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Edited by Xiaodong Wang, University of Texas Southwestern Medical Center, Dallas, TX, and approved January 13, 2006 (received for review July 29, 2005)
Abstract
Genetic tractability and easy manipulation make Caenorhabditis elegans a good model to study host–pathogen interactions. Dozens of different bacterial species can pathogenically infect C. elegans under laboratory conditions, and all of these microbes are extracellular pathogens to nematodes. Viruses, on the other hand, are obligate intracellular parasites, and yet no viral infections have been reported for C. elegans. We established a procedure allowing vaccinia virus to enter and subsequently replicate in C. elegans. Virus replication was significantly enhanced in ced-3, ced-4, ced-9(gf), and egl-1(lf) mutants, demonstrating that the core programmed cell death (PCD) genes ced-3, ced-4, ced-9, and egl-1 control vaccinia virus replication in C. elegans. The ability of ced-3 and ced-4 alleles to restrict virus replication is correlated with their cell-killing activities. Moreover, the increase in vaccinia virus replication levels in the PCD-defective mutants was not likely to be caused by the extra live cells, as neither the inhibition of PCD by icd-1 overexpression nor the presence of extra cells after extra cell divisions in cul-1 or lin-23 mutants had any significant effect on vaccinia virus replication. Therefore, the core PCD genes possess a unique function in controlling vaccinia virus replication in C. elegans.
Footnotes
- ‖To whom correspondence may be addressed. E-mail: chinglen{at}ms1.hinet.net or yichun{at}ntu.edu.tw
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Author contributions: W.-H.L., Y.-L.L., Y.-C.W., and C.-L.L. designed research; W.-H.L., J.-P.W., and W.L. performed research; W.L. contributed new reagents/analytic tools; W.-H.L., Y.-L.L., J.-P.W., W.L., R.F.H., Y.-C.W., and C.-L.L. analyzed data; and W.-H.L., Y.-C.W., and C.-L.L. wrote the paper.
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Conflict of interest statement: No conflicts declared.
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This paper was submitted directly (Track II) to the PNAS office.
- Abbreviations:
- PEG,
- polyethylene glycol;
- VV,
- vaccinia virus;
- PCD,
- programmed cell death;
- pfu,
- plaque-forming unit;
- p.i.,
- postinfection
Abbreviations:
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Freely available online through the PNAS open access option.
- © 2006 by The National Academy of Sciences of the USA
