Exploring Cell-to-Cell Transmission of the Dengue Virus between Mosquito Cells

The dengue virus is transmitted by mosquitoes between humans in nature, making it capable of infecting cells derived from both organisms. However, unlike in mammalian cells which frequently end up with apoptosis after infection, the virus usually causes persistent infection in mosquito cells. In the cell culture system, cells are usually infected via the regular receptor-dependent endocytosis after progeny virions are released from the infected cells. Cells containing progeny virions are eventually released and become the source of infection for other cells. In live mosquitoes, the ingested virus actually establishes infection in the midgut which is the first site of tissues susceptible to the virus infection. Subsequently, more progeny virions may be produced and extensively spread to neighboring areas, particularly salivary glands. However, cells in mosquito tissues are neatly arranged in dense. Progeny virions may not be able to infect other cells via release-and-infect approach. According to our previous observation, cell-to-cell transmission may one possible route for virus spread in tissues. In turn, this proposal aims to observe and demonstrate how the dengue virus infects neighboring cells by using various techniques in relation to cell biology and molecular biology. In mosquito cells infected by the dengue virus, we have previously identified several molecules including C189, eIF5A, GST, and eIF4EBP, which were up-regulated in response to the virus infection. C189 is a newly identified tetraspanin and was demonstrated not to serve as a receptor for DENV to infect mosquito cells as it was reported CD81 (another tetraspanin expressed on the liver cell) for hepatitis C virus. In contrast, overexpression of C189 was observed to exist with viral proteins concurrently and usually target the plasma membrane of infected cells, presumably beneficial or essential for cell-to-cell spread of the virus due to the role of tetraspanins demonstrated in intercellular adhesion. Accordingly, this study is expected to accomplish the goal, demonstrating whether and how this tetraspanin is involved in intracellular transportation as well as intercellular transmission of the progeny viral particles, e.g., cell-to-cell spread. This novel idea is particularly worthwhile to account for the virus spread between mosquito cells, especially for those cells constituted in mosquito tissues. This feature may also elucidate how mosquitoes are able to effectively transmit the dengue virus and probably other arboviruses in nature.

Project ID:PC10308-0671
External Project ID:MOST103-2320-B182-029-MY3