title: HIV-1 gp41 ectodomain enhances Cryptococcus neoformans binding to human brain microvascular endothelial cells via gp41 core-induced membrane activities.
abstract: Cryptococcus neoformans causes life-threatening meningoencephalitis, particularly prevalent in AIDS patients. The interrelationship between C. neoformans and HIV-1 is intriguing, as both pathogens elicit severe neuropathological complications. We have previously demonstrated that the HIV-1 gp41 ectodomain fragments gp41-I33 (amino acids 579-611) and gp41-I90 (amino acids 550-639) can enhance C. neoformans binding to HBMECs (human brain microvascular endothelial cells). Both peptides contain the loop region of gp41. In the present study, we used immunofluorescence microscopy and transmission and scanning electron microscopy to explore the underlying mechanisms. Our findings indicated that both C. neoformans and gp41-I90 up-regulated ICAM-1 (intercellular adhesion molecule 1) on the HBMECs and elicited membrane ruffling on the surface of HBMECs. The HIV-1 gp41 ectodomain could also induce CD44 and β-actin redistribution to the membrane lipid rafts, but it could not enhance PKCα (protein kinase Cα) phosphorylation like C. neoformans. Instead, gp41-I90 was able to induce syncytium formation on HBMECs. The results of the present study suggest HIV-1 gp41-enhanced C. neoformans binding to HBMECs via gp41 core domain-induced membrane activities, revealing a potential mechanism of invasion for this pathogenic fungus into the brain tissues of HIV-1-infected patients.
authors.affiliation: Division of Infectious Diseases, Saban Research Institute, Childrens Hospital Los Angeles, University of Southern California, Keck School of Medicine, Los Angeles, CA 90027, USA.
authors.forename: Sheng-He
authors.initials: SH
authors.lastname: Huang
authors.forename: Chu-Hua
authors.initials: CH
authors.lastname: Wu
authors.forename: Shibo
authors.initials: S
authors.lastname: Jiang
authors.forename: Ingrid
authors.initials: I
authors.lastname: Bahner
authors.forename: Albert S
authors.initials: AS
authors.lastname: Lossinsky
authors.forename: Ambrose Y
authors.initials: AY
authors.lastname: Jong
mesh_terms: D000199:Actins / Q000378:metabolism; D001665:Binding Sites; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000382:microbiology*; D002462:Cell Membrane / Q000378:metabolism* / Q000382:microbiology; D002478:Cells, Cultured; D003453:Cryptococcosis / Q000378:metabolism; D003455:Cryptococcus neoformans / Q000502:physiology*; D042783:Endothelial Cells / Q000378:metabolism / Q000382:microbiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000382:microbiology*; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D009154:Mutation; D051571:Protein Kinase C-alpha / Q000378:metabolism
chemical_list: D000199:Actins; D015700:HIV Envelope Protein gp41; C514787:gp41 protein, Human immunodeficiency virus 1; D018799:Intercellular Adhesion Molecule-1; D051571:Protein Kinase C-alpha