Dual effect of interleukin 4 on HIV-1 expression: implications for viral phenotypic switch and disease progression.
We report that interleukin 4 (IL-4) inhibits the propagation of non-syncytia-inducing and increases the propagation of syncytia-inducing HIV-1 isolates by two mechanisms. It differentially regulates the two major HIV-1 coreceptors, CCR5 and CXCR4, in human peripheral blood mononuclear cells, increasing CXCR4 and decreasing CCR5 expression in primary CD4(+) T-lymphocytes. In addition, IL-4 stimulates the expression of all HIV-1 isolates via a transcriptional activation mechanism. The combination of these effects results in increased propagation of CXCR4-using and inhibition of CCR5-using HIV-1 strains. IL-4 also activates HIV-1 expression in primary monocytes/macrophages but does not affect CCR5 expression. These results identify IL-4 as an important regulator of HIV-1 and suggest a critical role for this cytokine in the control of viral evolution and in the phenotypic switch from non-syncytia-inducing to syncytia-inducing, which leads to accelerated disease progression.
Valentin
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A
Human Retrovirus Section Advanced BioSciences Laboratories-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702-1201, USA.
Lu
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W
Rosati
M
M
Schneider
R
R
Albert
J
J
Karlsson
A
A
Pavlakis
G N
GN
D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D003001:Cloning, Molecular; D018450:Disease Progression; D015726:Giant Cells; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D008264:Macrophages / Q000821:virology; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019713:Receptors, CCR5 / Q000235:genetics; D014158:Transcription, Genetic
D012333:RNA, Messenger; D019713:Receptors, CCR5; D015847:Interleukin-4