To investigate the role of PTEN protein in dengue virus type 2 (DENV­2) infection and the related autophagy process, human umbilical vein endothelial cells (HUVECs) were challenged with the virus. PTEN expression and autophagy were checked by Western blotting and the level of LC3 type conversions respectively. The pLenti­PTEN and pLenti­shPTEN expression plasmids were constructed and packaged into lentiviruses to establish PTEN­ and shPTEN­expressing HUVEC cell lines for further detecting the effects of PTEN overexpression and downexpression on autophagy, especially ratio of LC3II/LC3I. The effects of PTEN on DENV­2 capsid expression and mRNA level as well as infectivity of progeny viruses were also examined. The data showed that the downexpression of PTEN inhibited autophagy and as a result, reduced the expression of DENV­2 capsid protein and the release of progeny virus particles. It is suggested that the downexpression of PTEN by DENV­2 infection in HUVECs is likely a host protective response against dengue virus infection.