This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pacciarini, F.
Right arrow Articles by Vicenzi, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pacciarini, F.
Right arrow Articles by Vicenzi, E.

 Previous Article  |  Next Article 

Journal of Virology, June 2008, p. 5137-5144, Vol. 82, No. 11
0022-538X/08/$08.00+0     doi:10.1128/JVI.00096-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Persistent Replication of Severe Acute Respiratory Syndrome Coronavirus in Human Tubular Kidney Cells Selects for Adaptive Mutations in the Membrane Protein{triangledown}

Filippo Pacciarini,1,{dagger} Silvia Ghezzi,1,{dagger} Filippo Canducci,2,6 Amy Sims,3 Michela Sampaolo,2,6 Elena Ferioli,5 Massimo Clementi,2,6 Guido Poli,4,6 Pier Giulio Conaldi,7 Ralph Baric,3 and Elisa Vicenzi1*

Viral Pathogens and Biosafety Unit, San Raffaele Scientific Institute, Milano, Italy,1 Laboratory of Microbiology and Virology, San Raffaele Scientific Institute, Milano, Italy,2 University of North Carolina at Chapel Hill, Chapel Hill, North Carolina,3 AIDS Immunopathogenesis Unit, San Raffaele Scientific Institute, Milano, Italy,4 Department of Medicine and Public Health, University of Insubria, Varese, Italy,5 Vita-Salute San Raffaele University, School of Medicine, Milano, Italy,6 Laboratory of Clinical Pathology, Microbiology and Virology, Mediterranean Institute for Transplantation and Advanced Specialised Therapies, University of Pittsburgh Medical Center—Italy, Palermo, Italy7

Received 15 January 2008/ Accepted 13 March 2008

Severe acute respiratory syndrome (SARS) is a systemic disease characterized by both lung pathology and widespread extrapulmonary virus dissemination causing multiple organ injuries. In this regard, renal dysfunction is an ominous sign in patients with SARS. Indeed, clusters of SARS coronavirus (SARS-CoV) particles have been detected in the cytoplasm of renal tubular epithelial cells in postmortem studies, explaining the presence of infectious virus in the urine of SARS patients. In order to investigate the potential SARS-CoV kidney tropism, we have evaluated the susceptibility of human renal cells of tubular and glomerular origin to in vitro SARS-CoV infection. Immortalized cultures of differentiated proximal tubular epithelial cells (PTEC), glomerular mesangial cells (MC), and glomerular epithelial cells (podocytes) were found to express the SARS-CoV receptor angiotensin-converting enzyme 2 on their surface. Productive infection, however, occurred only in PTEC but not in glomerular cells. A transient infection with poor virus production was observed in MC, whereas podocytes were not permissive to SARS-CoV infection. In contrast to the cytopathic infection of the Vero E6 cell line, SARS-CoV did not cause overt cytopathic effects in PTEC or MC. Of interest, PTEC, but not MC, maintained stable levels of SARS-CoV production in serial subcultures, suggesting a persistent state of infection. In this regard, a SARS-CoV variant with increased replication capacity in PTEC was selected after four serial subculture passages. This SARS-CoV variant acquired a single nonconservative amino acid change from glutamic acid (E) to alanine (A) at position 11 in the viral membrane (M) protein. The E11A point mutation was sufficient for enhanced SARS-CoV replication and persistence in PTEC when introduced in a SARS-CoV recombinant infectious clone. These findings indicate that human PTEC may represent a site of SARS-CoV productive and persistent replication favoring the emergence of viral variants with increased replication capacity, at least in these kidney cells.

* Corresponding author. Mailing address: P2/P3 Laboratories, DIBIT, Via Olgettina, 58, 20132 Milano, Italy. Phone: 39-02-2643-4908. Fax: 39-02-2643-4905. E-mail: vicenzi.elisa{at}hsr.it

{triangledown} Published ahead of print on 26 March 2008.

{dagger} F.P. and S.G. contributed equally to this work.

Journal of Virology, June 2008, p. 5137-5144, Vol. 82, No. 11
0022-538X/08/$08.00+0     doi:10.1128/JVI.00096-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Siu, K.-L., Kok, K.-H., Ng, M.-H. J., Poon, V. K. M., Yuen, K.-Y., Zheng, B.-J., Jin, D.-Y. (2009). Severe Acute Respiratory Syndrome Coronavirus M Protein Inhibits Type I Interferon Production by Impeding the Formation of TRAF3{middle dot}TANK{middle dot}TBK1/IKK{epsilon} Complex. J. Biol. Chem. 284: 16202-16209 [Abstract] [Full Text]  
  • Frieman, M., Baric, R. (2008). Mechanisms of Severe Acute Respiratory Syndrome Pathogenesis and Innate Immunomodulation. Microbiol. Mol. Biol. Rev. 72: 672-685 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»