title: HIV-1 gp41 ectodomain enhances Cryptococcus neoformans binding to HBMEC.
abstract: Cryptococcus neoformans infection has significantly increased recently, particularly in AIDS patients and immunocompromised individuals. C. neoformans has a predilection to the brain, resulting in devastating meningoencephalitis. We have previously shown the invasion of C. neoformans into the human brain microvascular endothelial cells (HBMEC), which constitute the blood-brain barrier. Here, we demonstrated that C. neoformans invasion of HBMEC was enhanced by HIV-1 gp41 protein. Peptide mapping defined its functional domain around the disulfide-bond linkage of gp41 molecule (a.a. 579-611). Recombinant protein gp41-I90 (a.a. 550-639) can also enhance the binding activity. The enhancement of C. neoformans binding to HBMEC is a strain-independent manner, suggesting that gp41 ectodomain peptide exerts its function directly on HBMEC. Importantly, the enhancement could be observed in mouse animal model. Our results suggest that HIV-1 gp41 ectodomain and C. neoformans may follow a similar invasion mechanism, possibly actin reorganization and/or membrane activation, during pathogen infections on HBMEC.
authors.affiliation: Division of Hematology-Oncology, Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA, and Department of Life Science, Catholic Fu-Jen University, Taiwan, ROC. ajong@chla.usc.edu
authors.forename: Ambrose Y
authors.initials: AY
authors.lastname: Jong
authors.forename: Chu-Hua
authors.initials: CH
authors.lastname: Wu
authors.forename: Shibo
authors.initials: S
authors.lastname: Jiang
authors.forename: Luo
authors.initials: L
authors.lastname: Feng
authors.forename: Han-Min
authors.initials: HM
authors.lastname: Chen
authors.forename: Sheng-He
authors.initials: SH
authors.lastname: Huang
mesh_terms: D001921:Brain / Q000098:blood supply* / Q000382:microbiology*; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation / Q000502:physiology*; D003455:Cryptococcus neoformans / Q000502:physiology*; D042783:Endothelial Cells / Q000382:microbiology*; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008833:Microcirculation / Q000382:microbiology*; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D015700:HIV Envelope Protein gp41