Dengue serotypes 1–4 exhibit unique host specificity in vitro

Kelli L Barr, Benjamin D Anderson, Gary L Heil, John A Friary, Gregory C Gray, Dana A Focks

Department of Environmental and Global Health, College of Public Health and Health Professions and the Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA

Background: Over 3000 cell lines from over 150 species are commercially available today from the American Type Culture Collection. These cell lines offer alternative approaches to investigating the interactions between arboviruses and other vertebrates at the cellular level. The various cell origins, types, and morphologies can be valuable resources for studying viral ecology and examining hypotheses regarding viral reservoirs. Dengue viruses (DENV) are major re-emerging pathogens that have been studied classically in only a few cell lines.
Methods: We evaluated the susceptibility of 19 distinct mammalian, avian, and reptilian cell lines to DENV infection. Cell lines were infected with DENV serotypes 1–4 and evaluated for susceptibility via focus-forming unit assays and quantitative reverse-transcription polymerase chain reaction.
Results: Both methods demonstrated the ability of DENV to replicate in 14 cell lines derived from various vertebrates with viral titers ranging from 1 × 10³ to 1 × 10⁷ infectious units per milliliter. Cell line susceptibility to DENV infection was serotype specific, with DENV-1 and DENV-4 infecting more cell lines than either DENV-2 or DENV-3. Cellular type also seemed to affect the infectivity of DENV. Human endothelial cells were only susceptible to DENV-4. Of six fibroblast lines, 100% were susceptible to at least one DENV serotype whereas only 62% of 13 epithelial lines were susceptible to DENV serotypes 1–4.
Conclusion: These data indicate that a variety of cell lines from human and animal species can be used to culture DENV. The serotype-specific susceptibility for certain cell lines may provide a tool to help characterize specific DENV serotypes as well as an in vitro platform for the study of host–pathogen interactions and the co-circulation of DENV serotypes in a specific region or individual.

Keywords: dengue virus, cell culture, host