STUDY OF DENGUE VIRUS-INFECTION IN SCID MICE ENGRAFTED WITH HUMAN K562 CELLS

Here we report that severe combined immunodeficient (SCID) mice engraf ted with human K562 cells (K562-SCID mice) can be used as an animal mo del to study dengue virus (DEN) infection. After intratumor injection into K562 cell masses of PL016, a Taiwanese DEN-2 human isolate, the K 562-SCID mice showed neurological signs of paralysis and died at appro ximately 2 weeks postinfection. In addition to being detected in the t umor masses, high virus titers were detected in the peripheral blood a nd the brain tissues, indicating that DEN had replicated in the infect ed K562-SCID mice. In contrast, the SCID mice were resistant to DEN in fection and the mock-infected K562-SCID mice survived for over 3 month s. These data illustrate that DEN infection contributed directly to th e deaths of the infected K562-SCID mice. Other serotypes of DEN,were a lso 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 whe ther a neutralizing antibody against DEN in vitro was also protective in vivo, the K562-SCID mice were challenged with DEN-2 and received an tibody administration at the same time or 1 day earlier. Our results r evealed that the antibody-treated mice exhibited a reduction in mortal ity and a delay of paralysis onset after DEN infection. In contrast to K562-SCID, the persistently DEN-infected K562 cells generated in vitr o invariably failed to be implanted in the mice. It seems that in the early stage of implantation, a gamma interferon activated, nitric oxid e-mediated anti-HEN effect might play a role in the innate immunity ag ainst HEN-infected cells. The system described herein offers an opport unity to explore DEN replication in vivo and to test various antiviral protocols in infected hosts.