title: Evidence of plasticity in the dengue virus: Host cell interaction.
abstract: Dengue virus (DENV) is the most important mosquito transmitted human viral pathogen. There are four different dengue viruses (DENV 1 to DENV 4) with multiple genotypes and strains. Whether there are significant differences in how these DENVs interact with and modulate the host cell proteome remains unclear. Using a panel of 12 DENVs representative of one isolate for each DENV from three different origins (lab adapted, low passage isolates from dengue fever patients, low passage isolates from dengue hemorrhagic fever patients) LLC-MK2 cells were equally infected and proteomic alterations compared by MALDI-TOF and principal component analysis and a sub-10 kDa peptidome analysis. There was no clear segregation of data with respect to either virus origin or serotype in either the MALDI-TOF or the peptidome analysis. The two isolates with the greatest variation from the other isolates in the MALDI-TOF analysis were a low passage DENV 3 dengue fever isolate and a low passage DENV 4 dengue hemorrhagic fever isolate. Analysis of the sub-10 kda protein fraction by LC-MS/MS identified 128 proteins of which only 28 (20%) were constantly expressed in all infections, while 80% showed variable expression, with no clear relationship with either serotype or virus origin. These results suggest that the interaction between DENV and the host cell is characterized by a degree of plasticity, whereby the end biological processes are not rigorously determined by specific proteome alterations, and that virus strain plays a role in determining the specific proteome changes.
authors.affiliation: Institute of Molecular Biosciences, Mahidol University, Bangkok, Thailand.
authors.forename: Chaiyot
authors.initials: C
authors.lastname: Rungruengphol
authors.affiliation: National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency, Pathum Thani, Thailand.
authors.forename: Janthima
authors.initials: J
authors.lastname: Jaresitthikunchai
authors.affiliation: Institute of Molecular Biosciences, Mahidol University, Bangkok, Thailand.
authors.forename: Nitwara
authors.initials: N
authors.lastname: Wikan
authors.affiliation: National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency, Pathum Thani, Thailand.
authors.forename: Narumon
authors.initials: N
authors.lastname: Phaonakrop
authors.affiliation: Institute of Molecular Biosciences, Mahidol University, Bangkok, Thailand.
authors.forename: Sujitra
authors.initials: S
authors.lastname: Keadsanti
authors.affiliation: Institute of Molecular Biosciences, Mahidol University, Bangkok, Thailand; Center for Emerging and Neglected Infectious Diseases, Mahidol University, Bangkok, Thailand.
authors.forename: Sutee
authors.initials: S
authors.lastname: Yoksan
authors.affiliation: National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency, Pathum Thani, Thailand.
authors.forename: Sittiruk
authors.initials: S
authors.lastname: Roytrakul
authors.affiliation: Institute of Molecular Biosciences, Mahidol University, Bangkok, Thailand; Center for Emerging and Neglected Infectious Diseases, Mahidol University, Bangkok, Thailand. Electronic address: duncan.smi@mahidol.ac.th.
authors.forename: Duncan R
authors.initials: DR
authors.lastname: Smith
mesh_terms: D000818:Animals; D002460:Cell Line; D003716:Dengue Virus / Q000502:physiology*; D054884:Host-Pathogen Interactions; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D020543:Proteome / Q000032:analysis*; D017422:Sequence Analysis, DNA; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D020543:Proteome
keywords: Dengue; LC-MS/MS; Low passage; Principal component analysis; Serotype