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Journal of Virology, February 2005, p. 2461-2473, Vol. 79, No. 4
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.4.2461-2473.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

The Proline-Rich Homeodomain (PRH/HEX) Protein Is Down-Regulated in Liver during Infection with Lymphocytic Choriomeningitis Virus

Mahmoud Djavani,1 Ivan Topisirovic,2 Juan Carlos Zapata,1 Mariola Sadowska,1 Yida Yang,1 Juan Rodas,1 Igor S. Lukashevich,1 Clifford W. Bogue,3 C. David Pauza,1 Katherine L. B. Borden,2 and Maria S. Salvato1*

Institute of Human Virology, University of Maryland Biotechnology Center, Baltimore, Maryland,1 Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York, New York,2 Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut3

Received 23 June 2004/ Accepted 28 September 2004

The proline-rich homeodomain protein, PRH/HEX, participates in the early development of the brain, thyroid, and liver and in the later regenerative processes of damaged liver, vascular endothelial, and hematopoietic cells. A virulent strain of lymphocytic choriomeningitis virus (LCMV-WE) that destroys hematopoietic, vascular, and liver functions also alters the transcription and subcellular localization of PRH. A related virus (LCMV-ARM) that does not cause disease in primates can infect cells without affecting PRH. Biochemical experiments demonstrated the occurrence of binding between the viral RING protein (Z) and PRH, and genetic experiments mapped the PRH-suppressing phenotype to the large (L) segment of the viral genome, which encodes the Z and polymerase genes. The Z protein is clearly involved with PRH, but other viral determinants are needed to relocate PRH and to promote disease. By down-regulating PRH, the arenavirus is able to eliminate the antiproliferative effects of PRH and to promote liver cell division. The interaction of an arenavirus with a homeodomain protein suggests a mechanism for viral teratogenic effects and for the tissue-specific manifestations of arenavirus disease.

* Corresponding author. Mailing address: Institute of Human Virology, University of Maryland Biotechnology Institute, 725 West Lombard St., Baltimore, MD 21201. Phone: (410) 706-1368. Fax: (410) 706-1992. E-mail: salvato{at}umbi.umd.edu.

Journal of Virology, February 2005, p. 2461-2473, Vol. 79, No. 4
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.4.2461-2473.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Djavani, M. M., Crasta, O. R., Zapata, J. C., Fei, Z., Folkerts, O., Sobral, B., Swindells, M., Bryant, J., Davis, H., Pauza, C. D., Lukashevich, I. S., Hammamieh, R., Jett, M., Salvato, M. S. (2007). Early Blood Profiles of Virus Infection in a Monkey Model for Lassa Fever. J. Virol. 81: 7960-7973 [Abstract] [Full Text]  
  • Bergthaler, A., Merkler, D., Horvath, E., Bestmann, L., Pinschewer, D. D. (2007). Contributions of the lymphocytic choriomeningitis virus glycoprotein and polymerase to strain-specific differences in murine liver pathogenicity. J. Gen. Virol. 88: 592-603 [Abstract] [Full Text]  
  • Garcia, C. C., Djavani, M., Topisirovic, I., Borden, K. L. B., Salvato, M. S., Damonte, E. B. (2006). Arenavirus Z protein as an antiviral target: virus inactivation and protein oligomerization by zinc finger-reactive compounds.. J. Gen. Virol. 87: 1217-1228 [Abstract] [Full Text]  


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