Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 19 November 2004:
Vol. 306. no. 5700, pp. 1380 - 1383
DOI: 10.1126/science.1103492
Prev | Table of Contents | Next

Reports

The Human Polyomavirus, JCV, Uses Serotonin Receptors to Infect Cells

Gwendolyn F. Elphick,1 William Querbes,1,2 Joslynn A. Jordan,1,2 Gretchen V. Gee,1,3 Sylvia Eash,1,2 Kate Manley,1,3 Aisling Dugan,1,2 Megan Stanifer,1,3 Anushree Bhatnagar,4 Wesley K. Kroeze,4 Bryan L. Roth,4 Walter J. Atwood1,2,3*

The human polyomavirus, JCV, causes the fatal demyelinating disease progressive multifocal leukoencephalopathy in immunocompromised patients. We found that the serotonergic receptor 5HT2AR could act as the cellular receptor for JCV on human glial cells. The 5HT2A receptor antagonists inhibited JCV infection, and monoclonal antibodies directed at 5HT2A receptors blocked infection of glial cells by JCV, but not by SV40. Transfection of 5HT2A receptor–negative HeLa cells with a 5HT2A receptor rescued virus infection, and this infection was blocked by antibody to the 5HT2A receptor. A tagged 5HT2A receptor colocalized with labeled JCV in an endosomal compartment following internalization. Serotonin receptor antagonists may thus be useful in the treatment of progressive multifocal leukoencephalopathy.

1 Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA.
2 Graduate Program in Pathobiology, Brown University, Providence, RI 02912, USA.
3 Graduate Program in Molecular Biology, Cellular Biology, and Biochemistry, Brown University, Providence, RI 02912, USA.
4 Department of Biochemistry, Case Western Reserve University Medical School, Cleveland, Ohio 44106, USA.

* To whom correspondence should be addressed. E-mail: Walter_Atwood{at}Brown.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
High-Throughput Cell-Based Screen for Chemicals That Inhibit Infection by Simian Virus 40 and Human Polyomaviruses.
E. C. Goodwin, W. J. Atwood, and D. DiMaio (2009)
J. Virol. 83, 5630-5639
   Abstract »    Full Text »    PDF »
Evidence for Distinct Antagonist-Revealed Functional States of 5-Hydroxytryptamine2A Receptor Homodimers.
J. Brea, M. Castro, J. Giraldo, J. F. Lopez-Gimenez, J. F. Padin, F. Quintian, M. I. Cadavid, M. T. Vilaro, G. Mengod, K. A. Berg, et al. (2009)
Mol. Pharmacol. 75, 1380-1391
   Abstract »    Full Text »    PDF »
Identification and Characterization of Mefloquine Efficacy against JC Virus In Vitro.
M. Brickelmaier, A. Lugovskoy, R. Kartikeyan, M. M. Reviriego-Mendoza, N. Allaire, K. Simon, R. J. Frisque, and L. Gorelik (2009)
Antimicrob. Agents Chemother. 53, 1840-1849
   Abstract »    Full Text »    PDF »
Mirtazapine Use in Human Immunodeficiency Virus-Infected Patients With Progressive Multifocal Leukoencephalopathy.
D. Cettomai and J. C. McArthur (2009)
Arch Neurol 66, 255-258
   Abstract »    Full Text »    PDF »
Progressive multifocal leucoencephalopathy associated with lupus and methotrexate overdose.
D Shprecher, T Frech, S Chin, R Eskandari, and J Steffens (2008)
Lupus 17, 1029-1032
   Abstract »    PDF »
Progressive multifocal leukoencephalopathy - the importance of early diagnosis illustrated in four cases.
O Nived, A. Bengtsson, A Jonsen, and G Sturfelt (2008)
Lupus 17, 1036-1041
   Abstract »    PDF »
Progressive Multifocal Leukoencephalopathy in a Patient With Relapsed Acute Myelogenous Leukemia.
S. Kesari, S. Akar, A. Saad, J. Drappatz, I. J. Koralnik, and D. J. DeAngelo (2008)
J. Clin. Oncol. 26, 3804-3807
   Full Text »    PDF »
Schizophrenia Susceptibility Genes Directly Implicated in the Life Cycles of Pathogens: Cytomegalovirus, Influenza, Herpes simplex, Rubella, and Toxoplasma gondii.
C.J. Carter (2008)
Schizophr Bull
   Abstract »    Full Text »    PDF »
Structural basis of GM1 ganglioside recognition by simian virus 40.
U. Neu, K. Woellner, G. Gauglitz, and T. Stehle (2008)
PNAS 105, 5219-5224
   Abstract »    Full Text »    PDF »
BK Virus Replication In Vitro: Limited Effect of Drugs Interfering with Viral Uptake and Intracellular Transport.
P. Randhawa, N. A. Farasati, and Y. Huang (2007)
Antimicrob. Agents Chemother. 51, 4492-4494
   Abstract »    Full Text »    PDF »
BK Virus Nephropathy and Kidney Transplantation.
D. L. Bohl and D. C. Brennan (2007)
Clin. J. Am. Soc. Nephrol. 2, S36-S46
   Abstract »    Full Text »    PDF »
Progressive multifocal leucoencephalopathy in a patient with sarcoidosis--successful treatment with cidofovir and mirtazapine.
K. Owczarczyk, R. Hilker, A. Brunn, M. Hallek, and A. Rubbert (2007)
Rheumatology 46, 888-890
   Full Text »    PDF »
Frequency and Phenotype of JC Virus-Specific CD8+ T Lymphocytes in the Peripheral Blood of Patients with Progressive Multifocal Leukoencephalopathy.
M. A. Lima, A. Marzocchetti, P. Autissier, T. Tompkins, Y. Chen, J. Gordon, D. B. Clifford, R. T. Gandhi, N. Venna, J. R. Berger, et al. (2007)
J. Virol. 81, 3361-3368
   Abstract »    Full Text »    PDF »
Potential Risk of Progressive Multifocal Leukoencephalopathy With Natalizumab Therapy: Possible Interventions.
O. Stuve, C. M. Marra, P. D. Cravens, M. P. Singh, W. Hu, A. Lovett-Racke, N. L. Monson, J. T. Phillips, J. W. C. Tervaert, R. A. Nash, et al. (2007)
Arch Neurol 64, 169-176
   Abstract »    Full Text »    PDF »
Functional Selectivity and Classical Concepts of Quantitative Pharmacology.
J. D. Urban, W. P. Clarke, M. von Zastrow, D. E. Nichols, B. Kobilka, H. Weinstein, J. A. Javitch, B. L. Roth, A. Christopoulos, P. M. Sexton, et al. (2007)
J. Pharmacol. Exp. Ther. 320, 1-13
   Abstract »    Full Text »    PDF »
Natalizumab and progressive multifocal leucoencephalopathy.
J R Berger (2006)
Ann Rheum Dis 65, iii48-iii53
   Abstract »    Full Text »    PDF »
A granule cell neuron-associated JC virus variant has a unique deletion in the VP1 gene.
X. Dang and I. J. Koralnik (2006)
J. Gen. Virol. 87, 2533-2537
   Abstract »    Full Text »    PDF »
Favourable outcome of progressive multifocal leucoencephalopathy in two patients with dermatomyositis..
S Vulliemoz, F Lurati-Ruiz, F-X Borruat, J Delavelle, I J Koralnik, T Kuntzer, J Bogousslavsky, F Picard, T Landis, and R A Du Pasquier (2006)
J. Neurol. Neurosurg. Psychiatry 77, 1079-1082
   Abstract »    Full Text »    PDF »
Human demyelinating disease and the polyomavirus JCV.
K Khalili and M K White (2006)
Multiple Sclerosis 12, 133-142
   Abstract »    PDF »
p90 ribosomal S6 kinase 2 exerts a tonic brake on G protein-coupled receptor signaling.
D. J. Sheffler, W. K. Kroeze, B. G. Garcia, A. Y. Deutch, S. J. Hufeisen, P. Leahy, J. C. Bruning, and B. L. Roth (2006)
PNAS 103, 4717-4722
   Abstract »    Full Text »    PDF »
Large-scale expression study of human mesial temporal lobe epilepsy: evidence for dysregulation of the neurotransmission and complement systems in the entorhinal cortex.
S. Jamali, F. Bartolomei, A. Robaglia-Schlupp, A. Massacrier, J.-C. Peragut, J. Regis, H. Dufour, R. Ravid, P. Roll, S. Pereira, et al. (2006)
Brain 129, 625-641
   Abstract »    Full Text »    PDF »
Involvement of Cytoskeletal Components in BK Virus Infectious Entry.
S. Eash and W. J. Atwood (2005)
J. Virol. 79, 11734-11741
   Abstract »    Full Text »    PDF »
INFECTION, INFLAMMATION, AND GASTROINTESTINAL CANCER.
C R Boland, M G Luciani, C Gasche, and A Goel (2005)
Gut 54, 1321-1331
   Full Text »    PDF »
Mining the Receptorome.
B. N. Armbruster and B. L. Roth (2005)
J. Biol. Chem. 280, 5129-5132
   Full Text »    PDF »
JC Virus Infects Cells via Serotonin Receptors.
(2004)
Journal Watch Infectious Diseases 2004, 7
   Full Text »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)