5890 Nucleic Acids Research, 2011, Vol. 39, No. 14 Figure 8. Mechanistic model showing HSF1-mediated regulation of HIV-1 transcription and replication by two distinct pathways. First pathway involves Nef-dependent activation of HSP40 promoter activity leading to increased viral gene expression as detailed in the text whereas the second pathway involves Nef independent direct activation of HIV-1 LTR promoter activity to increase viral gene expression and replication. directly interacting with newly identiﬁed HSF1 binding site on HIV-1 LTR independent of Nef (Figure 8). Increased expression, hyper-phosphorylation and incr- eased nuclear translocation of HSF1 in HIV-1-infected cells contribute to its enhanced activity. So our present work not only identiﬁes HSF1 as a pro-viral cellular factor but also provides a molecular mechanism for HSF1-mediated enhancement of viral gene expression and replication. Finally, the study also provides another example of how HIV-1 uses host cell proteins for its suc- cessful replication in the host and identiﬁes a possible anti-viral target for future studies. SUPPLEMENTARY DATA Supplementary Data are available at NAR Online. ACKNOWLEDGEMENTS We are thankful to Dr G.C. Mishra, Director, National Centre for Cell Science (NCCS) for his support and en- couragement. pNL4-3 plasmid, CEM-GFP cell line and Nef antiserum reagents were obtained from AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH. We thank Drs W.C. Greene, J. Goldman, J.C. Guatelli, T. Okamoto, K. Ohtsuka and M. Federico for providing different plasmids. We also thank Dr Manish Kumar for his technical support. FUNDING The Department of Biotechnology, Government of India; the National Centre for Cell Science, Pune. P.R. is a senior research fellow of the Department of Biotechnology, Government of India. Funding for open access charge: The Department of Biotechnology, Government of India; the National Centre for Cell Science, Pune. Conﬂict of interest statement. None declared. REFERENCES 1. Brenner,B.G. and Wainberg,Z. (2001) Heat shock proteins: novel therapeutic tools for HIV-infection? Expert. Opin. Biol. Ther., 1, 67–77. 2. Creagh,E.M., Sheehan,D. and Cotter,T.G. (2000) Heat shock proteins–modulators of apoptosis in tumour cells. Leukemia, 14, 1161–1173. 3. Takayama,S., Reed,J.C. and Homma,S. (2003) Heat-shock proteins as regulators of apoptosis. Oncogene, 22, 9041–9047. 4. van Eden,W., van der,Z.R. and Prakken,B. (2005) Heat-shock proteins induce T-cell regulation of chronic inﬂammation. Nat. Rev. Immunol., 5, 318–330. 5. Asea,A., Kraeft,S.K., Kurt-Jones,E.A., Stevenson,M.A., Chen,L.B., Finberg,R.W., Koo,G.C. and Calderwood,S.K. (2000)