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.
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Research Article|
August 26 2011
HIV-1 gp41 ectodomain enhances Cryptococcus neoformans binding to human brain microvascular endothelial cells via gp41 core-induced membrane activities
Sheng-He Huang;
Sheng-He Huang
*Division of Infectious Diseases, Saban Research Institute, Childrens Hospital Los Angeles, University of Southern California, Keck School of Medicine, Los Angeles, CA 90027, U.S.A.
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Chu-Hua Wu;
Chu-Hua Wu
†Division of Hematology-Oncology, Saban Research Institute, Childrens Hospital Los Angeles, University of Southern California, Keck School of Medicine, Los Angeles, CA 90027, U.S.A.
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Shibo Jiang;
Shibo Jiang
‡Key Laboratory of Medical Molecular Virology of MOE/MOH, Institute of Medical Microbiology, Shanghai Medical College, Fudan University, Shanghai 200032, China
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Ingrid Bahner;
Ingrid Bahner
§University of Southern Florida-College of Medicine, Department of Molecular Medicine, Tampa, FL 33612, U.S.A.
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Albert S. Lossinsky;
Albert S. Lossinsky
∥Department of Developmental Neurobiology, New York State Institute for Basic Research, Staten Island, NY 10314, U.S.A.
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Ambrose Y. Jong
Ambrose Y. Jong
1
†Division of Hematology-Oncology, Saban Research Institute, Childrens Hospital Los Angeles, University of Southern California, Keck School of Medicine, Los Angeles, CA 90027, U.S.A.
1To whom correspondence should be addressed (email ajong@chla.usc.edu).
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Publisher: Portland Press Ltd
Received:
January 31 2011
Revision Received:
June 03 2011
Accepted:
June 13 2011
Accepted Manuscript online:
June 13 2011
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biochem J (2011) 438 (3): 457–466.
Article history
Received:
January 31 2011
Revision Received:
June 03 2011
Accepted:
June 13 2011
Accepted Manuscript online:
June 13 2011
Citation
Sheng-He Huang, Chu-Hua Wu, Shibo Jiang, Ingrid Bahner, Albert S. Lossinsky, Ambrose Y. Jong; HIV-1 gp41 ectodomain enhances Cryptococcus neoformans binding to human brain microvascular endothelial cells via gp41 core-induced membrane activities. Biochem J 15 September 2011; 438 (3): 457–466. doi: https://doi.org/10.1042/BJ20110218
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