Hyperthermia Stimulates HIV-1 Replication

Abstract

HIV-infected individuals may experience fever episodes. Fever is an elevation of the body temperature accompanied by inflammation. It is usually beneficial for the host through enhancement of immunological defenses. In cultures, transient non-physiological heat shock (42–45°C) and Heat Shock Proteins (HSPs) modulate HIV-1 replication, through poorly defined mechanisms. The effect of physiological hyperthermia (38–40°C) on HIV-1 infection has not been extensively investigated. Here, we show that culturing primary CD4+ T lymphocytes and cell lines at a fever-like temperature (39.5°C) increased the efficiency of HIV-1 replication by 2 to 7 fold. Hyperthermia did not facilitate viral entry nor reverse transcription, but increased Tat transactivation of the LTR viral promoter. Hyperthermia also boosted HIV-1 reactivation in a model of latently-infected cells. By imaging HIV-1 transcription, we further show that Hsp90 co-localized with actively transcribing provirus, and this phenomenon was enhanced at 39.5°C. The Hsp90 inhibitor 17-AAG abrogated the increase of HIV-1 replication in hyperthermic cells. Altogether, our results indicate that fever may directly stimulate HIV-1 replication, in a process involving Hsp90 and facilitation of Tat-mediated LTR activity.

Application of magnetic field hyperthermia and superparamagnetic iron oxide nanoparticles to HIV-1-specific T-cell cytotoxicity

“…Since a recent publication demonstrated that hyperthermia increased HIV replication, any future experiments assessing the thermotherapeutic effects of nanoparticles in targeting of HIV-infected cells must be performed in the presence of HAART. 56 However, this study did not assess the potentially beneficial effect of thermotherapy to increase CTL killing of HIV antigenpresenting cells.…”

Heat Shock Protein 90 Facilitates Latent HIV Reactivation through Maintaining the Function of Positive Transcriptional Elongation Factor b (p-TEFb) under Proteasome Inhibition

“…Recently, we also revealed a key role for the active form of HSF1 in mediating latent HIV transcription and reactivation (9). Furthermore, HSP90 has been shown to control HIV reactivation from latency, by interacting with IKK and being involved in the degradation of IB␣ and NF-B translocation (10,11). Recently, Joshi et al (12) reported that inhibition of HSP90 prevents the recovery of HIV.…”

SAMHD1 Restricts HIV-1 Cell-to-Cell Transmission and Limits Immune Detection in Monocyte-Derived Dendritic Cells

“…Vesicular stomatitis virus G glycoprotein (VSV-G)-pseudotyped viruses and green fluorescent protein (GFP)-expressing lentiviral particles (LV-GFPs) were generated as described previously (38). SIV type 3 (SIV-3)-positive wild-type and the ⌬Vpx plasmids (a kind gift from Monsef Benkirane) were used to produce virion-like particles (VLPs) as described previously (7,39).…”