Hyperthermia Stimulates HIV-1 Replication

被引：53

作者：

Roesch, Ferdinand ^{[1
,2
]}

Meziane, Oussama ^{[4
,5
]}

Kula, Anna ^{[6
]}

Nisole, Sebastien ^{[7
]}

Porrot, Francoise ^{[1
,2
]}

Anderson, Ian ^{[8
]}

Mammano, Fabrizio ^{[3
,9
]}

Fassati, Ariberto ^{[8
]}

Marcello, Alessandro ^{[6
]}

Benkirane, Monsef ^{[4
,5
]}

Schwartz, Olivier ^{[1
,2
]}

机构：

[1] Inst Pasteur, Unite Virus & Immunite, Dept Virol, Paris, France

[2] CNRS, URA3015, Paris, France

[3] Univ Paris Diderot, IUH, UMRS 941, Paris, France

[4] Inst Genet Humaine, Mol Virol Lab, Montpellier, France

[5] CNRS, UPR1142, Montpellier, France

[6] ICGEB, Mol Virol Lab, Trieste, Italy

[7] Inst Pasteur, Unite Virol Mol & Vaccinol, Paris, France

[8] UCL, Wohl Vir Ctr, Div Infect & Immun, MRC Ctr Med & Mol Virol, London, England

[9] Hop St Louis, INSERM, U941, Paris, France

来源：

PLOS PATHOGENS | 2012年 / 8卷 / 07期

基金：

英国医学研究理事会;

关键词：

HUMAN-IMMUNODEFICIENCY-VIRUS; HEAT-SHOCK PROTEINS; HSP90 MOLECULAR CHAPERONE; CD4(+) T-CELLS; REVERSE-TRANSCRIPTASE; LATENT RESERVOIR; GENE-EXPRESSION; THERMAL-STRESS; ATP BINDING; TYPE-1;

D O I：

10.1371/journal.ppat.1002792

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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 degrees C) and Heat Shock Proteins (HSPs) modulate HIV-1 replication, through poorly defined mechanisms. The effect of physiological hyperthermia (38-40 degrees 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 degrees 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 degrees 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.

引用

页数：14

共 89 条

[1] Heat-shock protein 70 can replace viral protein R of HIV-1 during nuclear import of the viral preintegration complex [J].