Abstract
The effect of cGMP (cyclic GMP) dependent protein kinase 1-β (PKG1-β) and cGMP analogues on transcriptional activity and replication of human immunodeficiency virus type 1 (HIV-1) was investigated. Transfection of PKG1β expression plasmid increased expression from an HIV-1 LTR-reporter as well as from an infectious HIV-1 molecular clone, pNL4-3. Treatment of HIV-1 AD8-infected monocyte derived macrophages (MDMs) with cGMP agonists and cGMP antagonists caused respectively increased and decreased virus replication. These findings provide evidence that cGMP and PKG serve to regulate HIV-1 infection in human cells.
Highlights
Nitric oxide (NO) was postulated to have a negative effect on human immunodeficiency virus type 1 (HIV-1) replication through a cGMP-independent route [1]
It was not characterized as to how this cGMP-independent effect manifested mechanistically. It is well-accepted that a major intracellular signaling pathway for nitric oxide (NO) is through a cytosolic-guanylate cyclase linked cGMP-dependent protein kinase, PKG, pathway [2]. cGMP/PKG has been shown to activate abundantly both CREB [3] and NF-κB [4,5]
To our knowledge, no systematic investigation of cGMP/PKG's activity on the HIV-1 LTR has been reported to date
Summary
Nitric oxide (NO) was postulated to have a negative effect on HIV-1 replication through a cGMP-independent route [1]. To our knowledge, no systematic investigation of cGMP/PKG's activity on the HIV-1 LTR has been reported to date. To address how cGMP/PKG might influence HIV-1 LTRdirected expression, we transfected HeLa cells with a LTRluciferase reporter with or without a Tat-plasmid [6-9]and assayed for expression with or without simultaneously co-transfecting a PKG1β-expression vector [10](Figure 1). We found that PKG1β-alone activated reporter expression by approximately 4 fold ( see Figure 2B)
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