Replication in Cells of Hematopoietic Origin is Necessary for Dengue Virus Dissemination

Alissa M. Pham, Ryan A. Langlois, Benjamin R. tenOever

PLoS Pathog. 2012; 8(1): e1002465.

Speaker: Ming-Che, Tsai (蔡明哲)                              Time: 15:00~16:00, JAN. 8, 2014

Commentator: Dr. Hsiao-Sheng Liu (劉校生 博士)    Place: Room 601

Abstract:

   Dengue is induced by dengue virus infection and is a disease transmitted by the bite of mosquitoes carrying the virus. Patients infected with dengue virus have a potential to progress to fatal symptoms such as dengue hemorrhagic fever and dengue shock syndrome. There is no specific treatment for dengue other than supportive care with close monitoring which is the current practice. Although previous studies had been showed some of cells could be infected by dengue, it remains unclear which type of cells serve as virus reservoirs, and which cells are responsible for the virus spread. The current research is mainly focused on the effects of excluding DENV infection from hematopoietic cells through exploitation of the host microRNA (miRNA) machinery, and determining whether DENV replication could still be harbored in the absence of its major cell targets. In this study, hematopoietic-specific microRNA-142 (miR-142) was exploited to control virus tropism by inserting tandem target sites into the virus and to restrict replication in these cell populations, while both non-hematopoietic and hematopoietic cell lines were infected with DV. It was selectively attenuated in a cell-type specific manner. In vivo (infar1^-/- and Il28^-/- mice) use of this virus hindered the infection rate of CD11b⁺, CD11c⁺, and CD45⁺ cells, resulting in reduced virus spread, regardless of the route of administration. Furthermore, in vivo sequencing data showed that total excision of the inserted miR-142 target site in hematopoietic cells. This work demonstrates the importance of hematopoietic cells for DENV replication, and also is a good model to study for the properties of virus dissemination.

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