Dengue viruses exhibit strain-specific infectivity and entry requirements in vitro

Kelli L Barr, Benjamin D Anderson Department of Environmental and Global Health, College of Public Health and Health Professions and the Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA Background: Globally, dengue viruses (DENV) are the most common human arboviral infection and the most important public health threat from mosquito-borne viral pathogens. Recent work has indicated that DENV affinity for cell lines is serotype-specific, which raises challenging questions regarding DENV-host interactions as well as the development of therapeutics and control programs. Methods: We evaluated the infectious capacity of 11 strains of DENV for serotypes 1–4 in 17 distinct cell lines. The cell lines were evaluated for virus susceptibility via immunohistochemistry and quantitative reverse transcription polymerase chain reaction. Results: Both methods demonstrated the ability of DENV to replicate in all cell lines, with viral titers ranging from 1 × 102 to 1 × 107 infectious units per mL. Cell line susceptibility to DENV infection was strain-specific, with DENV-4 strains infecting more cell lines than the other serotypes. DENV-2 New Guinea C and DENV-4 H241 were detected in more cell lines than any other strains. Viral fusion assays indicated that DENV requirements for fusion are strain-specific. Conclusion: These data indicate that several cell lines can be used to culture and study DENV. The strain-specific susceptibility for certain cell lines may provide a tool for characterizing specific DENV strains and an in vitro platform for the development and optimization of therapeutics, the study of host-pathogen interactions, and ecological studies on the cocirculation of DENV strains in a specific region or individual. Keywords: dengue virus, cell culture, host, fusion