The DOI matches its Crossref record; 52 of the 54 references it cites were found in a registry or an index.
Reversal of West Nile virus-induced blood–brain barrier disruption and tight junction proteins degradation by matrix metalloproteinases inhibitor
Open accessAbstract
Though compromised blood-brain barrier (BBB) is a pathological hallmark of WNV-associated neurological sequelae, underlying mechanisms are unclear. We characterized the expression of matrix metalloproteinases (MMP) in WNV-infected human brain microvascular endothelial cells (HBMVE) and human brain cortical astrocytes (HBCA), components of BBB and their role in BBB disruption. Expression of multiple MMPs was significantly induced in WNV-infected HBCA cells. Naïve HBMVE cells incubated with the supernatant from WNV-infected HBCA cells demonstrated loss of tight junction proteins, which were rescued in the presence of MMP inhibitor, GM6001. Further, supernatant from WNV-infected HBCA cells compromised the in vitro BBB model integrity. Our data suggest astrocytes as one of the sources of MMP in the brain, which mediates BBB disruption allowing unrestricted entry of immune cells into the brain, thereby contributing to WNV neuropathogenesis. Because of the unavailability of WNV antivirals and vaccines, use of MMP inhibitors as an adjunct therapy to ameliorate WNV disease progression is warranted.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Viral infections in general downregulate TJ proteins and promote chemokine production and vascular cell adhesion molecule 1 (VCAM-1) expression in brain endothelial cells, thereby weakening the BBB and facilitating entry into the brain (5, 212, 399, 613).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [613]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis
Wang, T., Town, T., Alexopoulou, L., Anderson, J. F., Fikrig, E., & Flavell, R. A. (2004) · Nature Medicine · doi:10.1038/nm1140 · Cited by 1,142
Blood–brain Barrier: Structural Components and Function Under Physiologic and Pathologic Conditions
Persidsky, Y., Ramirez, S. H., Haorah, J., & Kanmogne, G. D. (2006) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-006-9025-3 · Cited by 922
Matrix metalloproteinases in neuroinflammation
Rosenberg, G. A. (2002) · Glia · doi:10.1002/glia.10108 · Cited by 868
Matrix metalloproteinase inhibitors as therapy for inflammatory and vascular diseases
Hu, J., den Steen, P. E. V., Sang, Q. A., & Opdenakker, G. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2308 · Cited by 806
Multiple roles for MMPs and TIMPs in cerebral ischemia
Cunningham, L. A., Wetzel, M. K., & Rosenberg, G. A. (2005) · Glia · doi:10.1002/glia.20169 · Cited by 412
West Nile Virus: Epidemiology and Clinical Features of an Emerging Epidemic in the United States
Hayes, E. B., & Gubler, D. J. (2005) · Annual Review of Medicine · doi:10.1146/annurev.med.57.121304.131418 · Cited by 366
Junctional complexes of the blood–brain barrier: permeability changes in neuroinflammation
Petty, M. A., & Lo, E. H. (2002) · Progress in Neurobiology · doi:10.1016/s0301-0082(02)00128-4 · Cited by 361
Vasogenic edema due to tight junction disruption by matrix metalloproteinases in cerebral ischemia
Rosenberg, G. A., & Yang, Y. R. (2007) · Neurosurgical FOCUS · doi:10.3171/foc.2007.22.5.5 · Cited by 358
A model for monocyte migration through the blood-brain barrier during HIV-1 encephalitis
Persidsky, Y., Stins, M. F., Way, D., Witte, M., Weinand, M. E., Kim, K. S., Bock, P., Gendelman, H. E., & Fiala, M. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.158.7.3499 · Cited by 316
Differential matrix metalloproteinase expression in cases of multiple sclerosis and stroke
Anthony, D. C., Ferguson, B., Matyzak, M. K., Miller, K., Esiri, M. M., & Perry, V. H. (1997) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.1997.tb01315.x · Cited by 268
Verma, S., Lo, Y. Y., Chapagain, M. L., Lum, S., Kumar, M., Gurjav, U., Luo, H., Nakatsuka, A. S., & Nerurkar, V. R. (2009) · Virology · doi:10.1016/j.virol.2008.11.047 · Cited by 267
Self-citationKim, Y. S., Kim, S. S., Cho, J. J., Choi, D. H., Hwang, O., Shin, D. H., Chun, H. S., Beal, M. F., & Joh, T. H. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.4346-04.2005 · Cited by 256
Leppert, D., Lindberg, R. L. P., Kappos, L., & Leib, S. L. (2001) · Brain Research Reviews · doi:10.1016/s0165-0173(01)00101-1 · Cited by 255
Matrix metalloproteinases and processing of pro-TNF-α
Gearing, A. J. H., Beckett, P., Christodoulou, M., Churchill, M., Clements, J. M., Crimmin, M., Davidson, A. H., Drummond, A. H., Gallowav, W. A., Gilbert, R. J. C., et al. (1995) · Journal of Leukocyte Biology · doi:10.1002/jlb.57.5.774 · Cited by 232
Kanmogne, G. D., Schall, K. A., Leibhart, J., Knipe, B., Gendelman, H. E., & Persidsky, Y. (2006) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600330 · Cited by 230
Gelatinase B modulates selective opening of the blood-brain barrier during inflammation
Mun-Bryce, S., & Rosenberg, G. A. (1998) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1998.274.5.r1203 · Cited by 230
Matrix Metalloproteinases in Brain Injury
Rosenberg, G. A. (1995) · Journal of Neurotrauma · doi:10.1089/neu.1995.12.833 · Cited by 225
JOHNATTY, R. N., Taub, D. D., Reeder, S., Turcovski‐Corrales, S. M., Cottam, D. W., Stephenson, T. J., & Rees, R. C. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.158.5.2327 · Cited by 205
Diamond, M., Shrestha, B., Mehlhop, E., Sitati, E. M., & Engle, M. J. (2003) · Viral Immunology · doi:10.1089/088282403322396082 · Cited by 197
Matrix Metalloproteinase 9 Facilitates West Nile Virus Entry into the Brain
Wang, P., Dai, J., Bai, F., Kong, K., Wong, S. J., Montgomery, R. R., Madri, J. A., & Fikrig, E. (2008) · Journal of Virology · doi:10.1128/jvi.00314-08 · Cited by 186
Clinical implications of matrix metalloproteinases
Mandal, M., Mandal, A., Das, S. K., Chakraborti, T., & Chakraborti, S. (2003) · Molecular and Cellular Biochemistry · doi:10.1023/a:1025526424637 · Cited by 173
Shigemori, Y., Katayama, Y., Mori, T., Maeda, T., & Kawamata, T. (2006) · Springer eBooks · doi:10.1007/3-211-30714-1_29 · Cited by 158
Arjona, A., Foellmer, H. G., Town, T., Leng, L., McDonald, C., Wang, T., Wong, S. J., Montgomery, R. R., Fikrig, E., & Bucala, R. (2007) · Journal of Clinical Investigation · doi:10.1172/jci32218 · Cited by 158
Elevation of matrix metalloproteinases (MMPs) in multiple sclerosis and impact of immunomodulators
Yong, V. W., Zabad, R., Agrawal, S., DaSilva, A. G., & Metz, L. M. (2007) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2006.11.021 · Cited by 156
Stromelysin‐1 (MMP‐3) is critical for intracranial bleeding after t‐PA treatment of stroke in mice
SUZUKI, Y., NAGAI, N., Umemura, K., Collen, D., & LIJNEN, H. R. (2007) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2007.02628.x · Cited by 152
Chaudhuri, A., Yang, B. Y., Gendelman, H. E., Persidsky, Y., & Kanmogne, G. D. (2007) · Blood · doi:10.1182/blood-2007-05-091207 · Cited by 147
Differential responses of human brain cells to West Nile virus infection
Cheeran, M. C. ‐., Hu, S., Sheng, W. S., Rashid, A., Peterson, P. K., & Lokensgard, J. R. (2005) · Journal of NeuroVirology · doi:10.1080/13550280500384982 · Cited by 145
Mahajan, S. D., Aalinkeel, R., Sykes, D. E., Reynolds, J. L., Bindukumar, B., Adal, A., Qi, M., Toh, J., Xu, G., Prasad, P. N., et al. (2008) · Brain Research · doi:10.1016/j.brainres.2008.01.093 · Cited by 139
van Marle, G., Antony, J. M., Ostermann, H., Dunham, C. P., Hunt, T. A., HALLIDAY, W. C., Maingat, F. G., Urbanowski, M. D., Hobman, T. C., Peeling, J., et al. (2007) · Journal of Virology · doi:10.1128/jvi.02422-06 · Cited by 128
Zozulya, A. L., Reinke, E. K., Baiu, D. C., Kármán, J., Sándor, M., & Fábry, Z. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.1.520 · Cited by 118
Qian, L., Xie, J., Ye, F., & Gao, S. (2007) · Journal of Virology · doi:10.1128/jvi.00016-07 · Cited by 99
Afonso, P. V., Ozden, S., Prévost, M., Schmitt, C., Seilhean, D., Weksler, B. B., Couraud, P., Antoine Gessain, A., Romero, I. A., & Ceccaldi, P. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.4.2576 · Cited by 97
West Nile virus: crossing the blood-brain barrier
Diamond, M., & Klein, R. S. (2004) · Nature Medicine · doi:10.1038/nm1204-1294 · Cited by 91
Ottino, P., Finley, J., Rojo–Niersbach, E. G., Ottlecz, A., Lambrou, G. N., Bazán, H. E. P., & Bazan, N. G. (2004) · PubMed · Cited by 85
Chapagain, M. L., Verma, S., Mercier, F., Yanagihara, R. T., & Nerurkar, V. R. (2007) · Virology · doi:10.1016/j.virol.2007.02.018 · Cited by 81
Self-citationWest Nile Virus Envelope Protein Inhibits dsRNA-Induced Innate Immune Responses
Arjona, A., Ledizet, M., Anthony, K., Bonafé, N., Modis, Y., Town, T., & Fikrig, E. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.12.8403 · Cited by 76
Production of MMPs in Human Cerebral Endothelial Cells and Their Role in Shedding Adhesion Molecules
Hummel, V., Kallmann, B. A., Wagner, S., Fuller, T., Bayas, A., Tonn, J.-C., Benveniste, E. N., Toyka, K. V., & Rieckmann, P. (2001) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/60.4.320 · Cited by 76
Sporer, B., Koedel, U., Paul, R. H., Kohleisen, B., Erfle, V., Fontana, A., & Pfister, H. (2000) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(99)00170-8 · Cited by 75
Sellner, J., Simon, F., Meyding‐Lamadé, U., & Leib, S. L. (2006) · Brain Research · doi:10.1016/j.brainres.2006.09.093 · Cited by 68
Stromelysin-1 and gelatinase A are upregulated before TNF-α in LPS-stimulated neuroinflammation
Mun-Bryce, S., Lukes, A., Wallace, J. A., Lukes-Marx, M., & Rosenberg, G. A. (2002) · Brain Research · doi:10.1016/s0006-8993(02)02303-x · Cited by 67
Rosenberg, G. A., Estrada, E. Y., & Mobashery, S. (2006) · Brain Research · doi:10.1016/j.brainres.2006.11.041 · Cited by 59
Diniz, J. A. P., da Rosa, A. P. A. T., Guzmán, H., Xu, F., Xiao, S., Popov, V. L., Vasconcelos, P. F. C., & Tesh, R. B. (2006) · American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.2006.75.691 · Cited by 58
Amantea, D., Russo, R., Gliozzi, M., Fratto, V., Berliocchi, L., Bagetta, G., Bernardi, G., & Corasaniti, M. T. (2007) · International review of neurobiology · doi:10.1016/s0074-7742(07)82008-3 · Cited by 57
Verma, S., Ziegler, K., Ananthula, P., Co, J. K. G., Frisque, R. J., Yanagihara, R. T., & Nerurkar, V. R. (2005) · Virology · doi:10.1016/j.virol.2005.10.012 · Cited by 51
Self-citationChua, P. K., Melish, M. E., Yu, Q., Yanagihara, R. T., Yamamoto, K., & Nerurkar, V. R. (2003) · Clinical and Vaccine Immunology · doi:10.1128/cdli.10.2.308-314.2003 · Cited by 49
Self-citationIn vitro effects of selenium deficiency on West Nile virus replication and cytopathogenicity
Verma, S., Molina, Y., Lo, Y. Y., Cropp, B. C., Nakano, C., Yanagihara, R. T., & Nerurkar, V. R. (2008) · Virology Journal · doi:10.1186/1743-422x-5-66 · Cited by 35
Self-citationConant, K. E., Haughey, N. J., Nath, A., Hillaire, C. S., Gary, D. S., Pardo, C. A., Wahl, L. M., Bilak, M. M., Milward, E. A., & Mattson, M. P. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.01038.x · Cited by 33
Chen, K., Liu, J.-Y., Lai, S., Hsu, L., & Lee, H.-H. (2006) · International Journal of Experimental Pathology · doi:10.1111/j.0959-9673.2006.00459.x · Cited by 28
Cheng, Y., King, N. J. C., & Kesson, A. M. (2004) · Virology · doi:10.1016/j.virol.2004.06.050 · Cited by 28
Keogh, B., Sheahan, B. J., Atkins, G. J., & Mills, K. H. G. (2003) · Veterinary Immunology and Immunopathology · doi:10.1016/s0165-2427(03)00082-5 · Cited by 13
Role for peroxisome proliferator-activated receptor-gamma in Alzheimer's disease.
van Geel (2001) · Open Repository and Bibliography (University of Luxembourg) · doi:10.1002/1531-8249(20010201)49:2 · Cited by 7
Kordower (1999) · doi:10.1002/1531-8249(199909)46:3
Flagged first, then by citations
2 of the 54 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Blood-Brain Barrier: From Physiology to Disease and Back
Sweeney, M. D., Zhao, Z., Montagne, A., Nelson, A. R., & Zlokovic, B. V. (2019) · Physiological Reviews · doi:10.1152/physrev.00050.2017 · Cited by 2,312
Modern methods for delivery of drugs across the blood–brain barrier
Chen, Y., & Liu, L. (2011) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2011.11.010 · Cited by 1,038
Virus Infections in the Nervous System
Koyuncu, O. O., Hogue, I. B., & Enquist, L. W. (2013) · Cell Host & Microbe · doi:10.1016/j.chom.2013.03.010 · Cited by 594
West Nile virus infection and immunity
Suthar, M. S., Diamond, M., & Gale, M. (2013) · Nature Reviews Microbiology · doi:10.1038/nrmicro2950 · Cited by 432
Occludin: One Protein, Many Forms
Cummins, P. M. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.06029-11 · Cited by 409
Metadata
- Authors
- Verma, S., Kumar, M., Gurjav, U., Lum, S., & Nerurkar, V. R.
- Affiliations
- University of Hawaiʻi at Mānoa (US)
- Corresponding author
- Nerurkar, Vivek R.
- Venue
- Virology
- Publisher
- Elsevier BV
- Published
- 2010-02
- Volume
- 397
- Issue
- 1
- Pages
- 130-138
- ISSN
- 0042-6822 (ISSN-L)
- PMC
- PMC3102050
- OpenAlex
- W1968754528
- Cited by
- 151
- References
- 54
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 14 · 2023: 5 · 2022: 7 · 2021: 13 · 2020: 6 · 2019: 7 · 2018: 7 · 2017: 9 · 2016: 5 · 2015: 15 · 2014: 14 · 2013: 9 · 2012: 16
- FWCI
- 5.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1262 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Virology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Hawaii Community Foundation (20050405)
- Research Centers in Minority Institutions Program (G12RR003061)
- Centers of Biomedical Research Excellence (P20RR018727)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Keywords
- West Nile virus, blood-brain barrier disruption, matrix metalloproteinases, tight junction proteins, astrocytes, brain microvascular endothelial cells, GM6001, matrix metalloproteinase inhibitors, neuroinflammation
- MeSH terms
- Astrocytes, Blood-Brain Barrier, Dipeptides, Humans, Membrane Proteins, Phosphoproteins, Protease Inhibitors, West Nile virus, Tight Junctions, Matrix Metalloproteinases, Gene Expression Profiling, Endothelial Cells, Matrix Metalloproteinase Inhibitors, Claudin-1, Zonula Occludens-1 Protein
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
