Ataxia-telangiectasia-mutated (ATM) protein can enhance human immunodeficiency virus type 1 replication by stimulating Rev function.
The ataxia-telangiectasia-mutated (ATM) kinase plays a central role in responses to various forms of DNA damage and has been suggested to facilitate human immunodeficiency virus type 1 (HIV-1) integration. Here, we describe a series of experiences that indicate that ATM can enhance HIV-1 replication by stimulating the action of the Rev viral posttranscriptional regulator. The Rev-dependent stimulation of viral late gene expression was observed with ATM-overexpressing cells, a result confirmed with a Rev-dependent reporter construct. Both parameters were also enhanced upon treatment of HeLa cells with caffeine, a xanthine that, in this cellular context, stimulates ATM activity. As well, decreased levels of virions with reduced infectivity were released by ATM knockdown cells. Notably, ATM overexpression did not stimulate the HIV-1 late gene expression within the context of Rev-independent constructs or the Rex-dependent production of capsid from human T-cell leukemia virus type 1 proviral constructs. Altogether, these results indicate that ATM can positively influence HIV-1 Rev function.
Department of Microbiology and Molecular Medicine, University of Geneva, Switzerland.
Yasuo
Y
Ariumi
Didier
D
Trono
D064007:Ataxia Telangiectasia Mutated Proteins; D002110:Caffeine; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015967:Gene Expression Regulation, Viral; D015694:Gene Products, rev / Q000502:physiology*; D020868:Gene Silencing; D017930:Genes, Reporter; D016655:HIV Core Protein p24 / Q000032:analysis; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication; D054321:rev Gene Products, Human Immunodeficiency Virus
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D015694:Gene Products, rev; D016655:HIV Core Protein p24; D025521:Tumor Suppressor Proteins; D054321:rev Gene Products, Human Immunodeficiency Virus; D002110:Caffeine; D008156:Luciferases; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases