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JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/01.qai.0000413808.02522.46
POSTER SESSION ABSTRACTS: PDF Only

E1 Molecular and Cellular Correlates of the CIITA-Mediated Inhibition of HTLV-2 Tax-2 Transactivator Function Resulting in Loss of Viral Replication.

Orlandi, Chiara; Forlani, Greta; Tosi, Giovanna; Accolla, Roberto S.

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Abstract

MHC class II transactivator CIITA inhibits the function of HTLV-2 Tax-2 viral transactivator and, consequently, the replication of the virus in infected cells. By co-immunoprecipitation of lysates from 293T cells cotransfected with CIITA or fragments of it, and Tax-2 it was found that the two factors interact in vivo. At least two CIITA regions, at the 1-252 N-term and at the 410-1130 C-term, respectively, interacted with Tax-2. Interestingly only the 1-252 N-term region mediated Tax-2 functional inhibition. CIITA and Tax-2 localized both in the cytoplasm and in the nucleus, when separately expressed. Instead, when coexpressed, most of Tax-2 colocalized with CIITA in cytoplasm around the nuclear membrane. Interestingly, when CIITA nucleus-cytoplasm shuttling were blocked by leptomycin B treatment, most of the Tax-2 molecules were also blocked and co-localized with CIITA in the nucleus, suggesting that CIITA-Tax-2 binding does not preclude Tax-2 entry into the nucleus. Finally, the nuclear factor NF-YB, also strongly binds to Tax-2. Notably, although endogenous NF-YB does not inhibit Tax-2-dependent HTLV-2 LTR transactivation, it still binds to Tax-2, and in presence of CIITA, this binding seems to increase.

These results strongly suggest that CIITA inhibit Tax-2 by binding the viral transactivator both directly or through a tripartite interaction with NF-YB. CIITA is therefore a viral restriction factor for HTLV-2 and this open the possibility to control HTLV-2 viral replication and spreading by the controlled induction of CIITA in infected cells.

(C) 2012 Lippincott Williams & Wilkins, Inc.

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