Abstract
HIV-1 Vpr plays a pivotal role in viral pathogenesis and is preferentially targeted by the host immune system. In this report, we demonstrate that a small heat shock protein, HSP27, exhibits Vpr-specific antiviral activity, as its expression is specifically responsive to vpr gene expression and increased levels of HSP27 inhibit Vpr-induced cell cycle G2 arrest and cell killing. We further show that overexpression of HSP27 reduces viral replication in T-lymphocytes in a Vpr-dependent manner. Mechanistically, Vpr triggers HSP27 expression through heat shock factor (HSF) 1, but inhibits prolonged expression of HSP27 under heat-shock conditions. Together, these data suggest a potential dynamic and antagonistic interaction between HIV-1 Vpr and a host cell HSP27, suggesting that HSP27 may contribute to cellular intrinsic immunity against HIV infection.
Highlights
Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr), a virionassociated protein with a calculated molecular weight of 12.7 kilodalton, is highly conserved among HIV, simian immunodeficiency virus (SIV), and other lentiviruses [1,2]
We further demonstrate that HSP27 production is responsive to vpr gene expression either alone or in the context of HIV infection
The mechanistic details of Vprdependent induction and restriction of HSF1 expression remain to be further delineated, our finding that vpr gene expression elicits HSF1 – but not HSF2mediated HSP27 activation suggests that Vpr triggers a cellular stress response that may involve HSF1mediated cellular events
Summary
Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr), a virionassociated protein with a calculated molecular weight of 12.7 kilodalton (kD), is highly conserved among HIV, simian immunodeficiency virus (SIV), and other lentiviruses [1,2]. Vpr displays several distinct activities in host cells and has been implicated in multiple virus-host interactions. These include induction of cell cycle G2 arrest [8] and cell killing [9]. The cell cycle G2 arrest induced by Vpr is thought to suppress human immune functions by preventing T cell clonal expansion [10] and to provide an optimized cellular environment to viral replication [3]. The biological role of Vpr-induced apoptosis of target cells is unclear at present, but may represent a host self-destructive mechanism to prevent viral spread or may be a viral mechanism to deplete CD4+ T-cells [7,11,12]
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