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Journal of Virology, December 1998, p. 9729-9737, Vol. 72, No. 12
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Study of Dengue Virus Infection in SCID Mice Engrafted with Human K562 Cells

Yi-Ling Lin,1,2,3,* Ching-Len Liao,2 Li-Kuang Chen,4 Chia-Tsui Yeh,4 Chiu-I Liu,3 Shiou-Hwa Ma,3 Yu-Ying Huang,3 Yue-Ling Huang,3 Chuan-Liang Kao,5 and Chwan-Chuen King6

Institute of Biomedical Sciences, Academia Sinica,1 Department of Microbiology and Immunology,2 and Institute of Preventive Medicine,3 National Defense Medical Center, Department of Immunology, Buddhist Tzu-chi Medical College,4 and Department of Medical Technology,5 and Institute of Epidemiology,6 National Taiwan University, Taipei, Taiwan, Republic of China

Received 7 April 1998/Accepted 9 September 1998

Here we report that severe combined immunodeficient (SCID) mice engrafted with human K562 cells (K562-SCID mice) can be used as an animal model to study dengue virus (DEN) infection. After intratumor injection into K562 cell masses of PL046, a Taiwanese DEN-2 human isolate, the K562-SCID mice showed neurological signs of paralysis and died at approximately 2 weeks postinfection. In addition to being detected in the tumor masses, high virus titers were detected in the peripheral blood and the brain tissues, indicating that DEN had replicated in the infected K562-SCID mice. In contrast, the SCID mice were resistant to DEN infection and the mock-infected K562-SCID mice survived for over 3 months. These data illustrate that DEN infection contributed directly to the deaths of the infected K562-SCID mice. Other serotypes of DEN were also used to infect the K562-SCID mice, and the mortality rates of the infected mice varied with different challenge strains, suggesting the existence of diverse degrees of virulence among DENs. To determine whether a neutralizing antibody against DEN in vitro was also protective in vivo, the K562-SCID mice were challenged with DEN-2 and received antibody administration at the same time or 1 day earlier. Our results revealed that the antibody-treated mice exhibited a reduction in mortality and a delay of paralysis onset after DEN infection. In contrast to K562-SCID, the persistently DEN-infected K562 cells generated in vitro invariably failed to be implanted in the mice. It seems that in the early stage of implantation, a gamma interferon activated, nitric oxide-mediated anti-DEN effect might play a role in the innate immunity against DEN-infected cells. The system described herein offers an opportunity to explore DEN replication in vivo and to test various antiviral protocols in infected hosts.

* Corresponding author. Mailing address: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan, Republic of China. Phone: (886)-2-2652-3902. Fax: (886)-2-2782-9224. E-mail: yll{at}ibms.sinica.edu.tw.

Journal of Virology, December 1998, p. 9729-9737, Vol. 72, No. 12
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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