Establishing Restricted Expression of Caveolin-1 in HIV Infected Cells and Inhibition of Virus Replication



Yung-Tsun Lo, Peter E Nadeau, Shanshan Lin , Ayalew Mergia*
Department of Infectious Disease and Pathology, University of Florida, Gainesville, FL 32611, USA


Article Metrics

CrossRef Citations:
4
Total Statistics:

Full-Text HTML Views: 315
Abstract HTML Views: 236
PDF Downloads: 80
Total Views/Downloads: 631
Unique Statistics:

Full-Text HTML Views: 204
Abstract HTML Views: 128
PDF Downloads: 60
Total Views/Downloads: 392



© Lo et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Department of Infectious Disease and Pathology, University of Florida, Gainesville, FL 32611, USA; Tel: (352)-294-4139; Fax: (352)-392-9704; E-mail: mergiaa@ufl.edu


Abstract

Background:

Caveolin-1 (Cav-1) is the major protein of the caveolae and plays a role in multiple cellular functions and implicated to have anti-HIV activity. Regulated expression of Cav-1 is important for safe and effective use in order to exploit Cav-1 for HIV therapeutic applications.

Methods:

A series of Cav-1 and GFP expression vectors were constructed under the control of the HIV LTR for conditional expression or CMV promoter and the expression of Cav-1 was monitored in the presence or absence of Tat or HIV infection in order to establish the restricted expression of Cav-1 to HIV infected cells.

Results:

Cav-1 expression was evident under the control of the HIV LTR in the absence of Tat or HIV infection as demonstrated by immunoblot. Placing two internal ribosomal entry sequences (IRES) and a Rev response element, RRE (5’~ LTR-IRES-GFP-RRE-IRES-Cav-1~3’) resulted in no expression of Cav-1 in the absence of Tat with effective expression in the presence of Tat. Transduction of HIV permissive cells with this construct using a foamy virus vector show that Cav-1 was able to inhibit HIV replication by 82%. Cells that received LTR-IRES-GFP-RRE-IRES-Cav-1 remain healthy in the absence of Tat or HIV infection.

Conclusion:

These results taken together reveal the inclusion of two IRES establishes a significant reduction of leak through expression of Cav-1 in the absence of Tat or HIV infection. Such regulated expression will have therapeutic application of Cav-1 for HIV infection as well as broad applications which can be beneficial for other host-targeted interventions as therapeutics.

Keywords: Caveolin-1, HIV, LTR, Tat.