Heat shock protein 90 and heat shock protein 70 are components of dengue virus receptor complex in human cells.
Dengue virus requires the presence of an unidentified cellular receptor on the surface of the host cell. By using a recently published affinity chromatography approach, an 84-kDa molecule, identified as heat shock protein 90 (HSP90) by matrix-assisted laser desorption ionization-time of flight mass spectrometry, was isolated from neuroblastoma and U937 cells. Based on the ability of HSP90 (84 kDa) to interact with HSP70 (74 kDa) on the surface of monocytes during lipopolysaccharide (LPS) signaling and evidence that LPS inhibits dengue virus infection, the presence of HSP70 was demonstrated in affinity chromatography eluates and by pull-down experiments. Infection inhibition assays support the conclusion that HSP90 and HSP70 participate in dengue virus entry as a receptor complex in human cell lines as well as in monocytes/macrophages. Additionally, our results indicate that both HSPs are associated with membrane microdomains (lipid rafts) in response to dengue virus infection. Moreover, methyl-beta-cyclodextrin, a raft-disrupting drug, inhibits dengue virus infection, supporting the idea that cholesterol-rich membrane fractions are important in dengue virus entry.
Reyes-Del Valle
Jorge
J
Departamento de Patología Experimental, Centro de Investigación y de Estudios Avanzados del IPN, Av. I.P.N. 2508, Col. San Pedro Zacatenco, Mexico City D.F., C.P. 07360, Mexico.
Chávez-Salinas
Salvador
S
Medina
Fernando
F
Del Angel
Rosa M
RM
D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003716:Dengue Virus / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis*; D018841:HSP90 Heat-Shock Proteins / Q000032:analysis*; D006801:Humans; D008264:Macrophages / Q000821:virology; D009000:Monocytes / Q000821:virology; D009447:Neuroblastoma; D011991:Receptors, Virus / Q000737:chemistry* / Q000302:isolation & purification; D020298:U937 Cells; D014779:Virus Replication
D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D011991:Receptors, Virus; C111476:dengue virus receptor