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Blood, 1 February 2004, Vol. 103, No. 3, pp. 995-1001. Prepublished online as a Blood First Edition Paper on October 2, 2003; DOI 10.1182/blood-2003-07-2503. This Article Full Text (PDF) All Versions of this Article: 2003-07-2503v1 103/3/995    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Casoli, C. Articles by Accolla, R. S Search for Related Content PubMed PubMed Citation Articles by Casoli, C. Articles by Accolla, R. S Social Bookmarking                   What's this? Submitted July 24, 2003 Accepted September 23, 2003 The MHC class II transcriptional activator (CIITA) inhibits HTLV-2 viral replication by blocking the function of the viral transactivator Tax-2 Claudio Casoli*, Andrea De Lerma Barbaro, Elisabetta Pilotti, Umberto Bertazzoni, Giovanna Tosi, and Roberto S Accolla Department of Clinical Medicine, Nephrology and Health Sciences, School of Medicine, University of Parma, Parma, Italy Department of Clinical and Biological Sciences, School of Medicine, University of Insubria, Varese, Italy Department of Mother and Child, Biology and Genetic Section, School of Medicine, University of Verona, Verona, Italy * Corresponding author; email: claudio.casoli{at}unipr.it. The human T-cell leukemia virus type 2 (HTLV-2), an oncogenic retrovirus closely related to HTLV-1, produces a lifelong infection whose possible association to certain human diseases is still debated. Although some viral products can influence the expression and action of cellular genes, very little is known about the molecular mechanisms involved. Here we show that the AIR-1-encoded human MHC class II transactivator CIITA strongly inhibits viral replication, but not virus entry, in human B- and T-cell susceptible targets. This effect results from CIITA inhibiting the Tax-mediated transactivation of the HTLV-2 LTR. Further molecular analysis shows that the N-terminal region of CIITA encompassing the first 321 amino acids, is responsible for the inhibitory effect on viral replication. This region is crucial for the transactivation of human MHC class II genes and includes the activation domain as well as domains interacting with co-activators which are also used by the viral transactivator Tax to modulate cellular functions. These results represent the first evidence that a cellular transcriptional activator, controlling the coordinate expression of the entire family of MHC class II antigen presenting molecules, inhibits HTLV-2 viral replication by a distinct mechanism. In this new role CIITA may represent a new tool for therapeutic strategies aimed at counteracting HTLV-2 replication and spreading. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Tosi, E. Pilotti, L. Mortara, A. D. L. Barbaro, C. Casoli, and R. S. Accolla Inhibition of human T cell leukemia virus type 2 replication by the suppressive action of class II transactivator and nuclear factor Y PNAS, August 22, 2006; 103(34): 12861 - 12866. [Abstract] [Full Text] [PDF] L. Meertens, S. Chevalier, R. Weil, A. Gessain, and R. Mahieux A 10-Amino Acid Domain within Human T-cell Leukemia Virus Type 1 and Type 2 Tax Protein Sequences Is Responsible for Their Divergent Subcellular Distribution J. Biol. Chem., October 8, 2004; 279(41): 43307 - 43320. [Abstract] [Full Text] [PDF]

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