Primary human endothelial cells support direct but not antibody-dependent enhancement of dengue viral infection.
Microvascular plasma leakage is the hallmark of dengue hemorrhagic fever and dengue shock syndrome. The precise molecular mechanisms leading to microvascular leakage are yet to be determined, but dengue virus (DENV) infection and consequent endothelial cell death has been suggested as its major cause. However, the extent of endothelial cell permissiveness to DENV infection and the magnitude of cell death following DENV infection are controversial. To clarify this issue, we analyzed the kinetics and consequences of DENV infection of human umbilical vein endothelial cells (HUVEC) using a novel molecularly cloned DENV2-16681 virus. Viral replication was detected as early as 24 hr post-infection by RT-PCR and plaque assays. However, merely 2% of HUVEC were DENV antigen-positive even after 96 hr of infection as measured by the FACS indirect immunofluorescence assays. Unlike monocytes/macrophages, HUVEC did not support antibody dependent enhancement of dengue viral infection due to a lack of FcgammaRI and FcgammaRII. Furthermore, DENV infection did not increase HUVEC apoptosis as compared to mock-infected cells. Because in vitro only a small percentage of endothelial cells were productively infected in vitro with no significant apoptosis occurring in either infected or bystander cells, it would be important to re-examine whether direct dengue viral infection of endothelium is the major cause of the extensive vascular leakage observed in patients with dengue hemorrhagic fever and dengue shock syndrome.
Arévalo
Maria T
MT
Department of Microbiology and Immunology, University of Rochester, New York 14642, USA.
Simpson-Haidaris
Patricia J
PJ
Kou
Zhihua
Z
Schlesinger
Jacob J
JJ
Jin
Xia
X
D019067:Antibody-Dependent Enhancement; D003716:Dengue Virus / Q000502:physiology*; D042783:Endothelial Cells / Q000821:virology*; D006801:Humans; D012367:RNA, Viral / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019595:Severe Dengue / Q000821:virology; D010948:Viral Plaque Assay; D014779:Virus Replication
D012367:RNA, Viral