Heat Shock Protein 70 Protects Cells from Cell Cycle Arrest and Apoptosis Induced by Human Immunodeficiency Virus Type 1 Viral Protein R

Abstract

Heat shock proteins (HSPs) are produced in cells in response to a range of stress-related stimuli, including heat, UV radiation, and microbial/viral infections. In addition to previously recognized activity of HSPs as facilitators of protein folding and chaperones, recent studies revealed unique properties of HSPs in generating specific immune responses against cancers and infectious agents (reviewed in reference 3). More-

Gene therapy progress and prospects: Novel gene therapy approaches for AIDS

“…A recent report involves the heatshock protein 70 (Hsp70) as a possible novel innate immunity factor against HIV-1. Hsp70 seems to block both G2 and apoptosis in a Vpr-dependent manner, 84 inhibiting the nuclear localization of Vpr. Interestingly, in Vpr-deficient HIV-1-infected macrophages, Hsp70 seems to have an opposite effect on nuclear import and replication.…”

Human immunodeficiency virus type 1 (HIV-1) Vpr-regulated cell death: insights into mechanism

“…59 In addition, HSP70 overexpression was also sufficient to attenuate both cell cycle arrest and apoptosis, and RNAi of HSP70 increased the sensitivity of host cells for apoptosis, cell cycle arrest, and viral replication. 60 The authors also purified Vpr in complex with HSP70 with the mild detergent CHAPS, suggesting that a direct or indirect interaction is involved. 59,60 A fascinating question that arises is whether this interaction is a direct or a complex involving certain adaptors form.…”

“…60 The authors also purified Vpr in complex with HSP70 with the mild detergent CHAPS, suggesting that a direct or indirect interaction is involved. 59,60 A fascinating question that arises is whether this interaction is a direct or a complex involving certain adaptors form. If a direct interaction is responsible, then it suggests that HSP70 perturbs Vpr's various functions by binding and nullifying it in a manner similar to a neutralizing antibody.…”

“…49 Lastly, investigations into the role of heat-shock proteins have determined that HSP70 is likely both necessary and sufficient to inhibit many of Vpr's destructive effects, which highlights its importance. 60 Despite these differences in complexes and targets, these studies do not preclude the potential of an inclusive model that requires all of these factors. It is also a possibility that each necessary component functions to initiate inductively apoptosis or potentiate the host to allow apoptosis to transpire.…”

Spermatocyte-specific expression of constitutively active heat shock factor 1 induces HSP70i-resistant apoptosis in male germ cells

“…Numerous studies, however, have shown that overexpression of HSP70, in either transgenic mice or transfected cells, can protect different somatic cells from apoptotic death induced not only by the hyperthermia 15 but also by other stimuli, including ischemia, 16 nitric oxide, 17 adriamycin, 18 UV-B radiation 19 or pathogenic viruses. 20 Two members of the HSP family are expressed normally under non-heat shock conditions specifically during spermatogenesis. Spermatocyte-specific HSP70, called HSP70.2 in mice and HST70 in rats, is expressed in pachytene spermatocytes during the meiotic phase.…”