title: Polymorphism in the interleukin-4 promoter affects acquisition of human immunodeficiency virus type 1 syncytium-inducing phenotype.
abstract: The emergence of syncytium-inducing (SI) variants of human immunodeficiency virus type 1 (HIV-1) in infected individuals is an indicator of poor prognosis and is often correlated with faster CD4(+) cell depletion and rapid disease progression. Interleukin-4 (IL-4) is a pleiotropic cytokine with various immune-modulating functions including induction of immunoglobulin E (IgE) production in B cells, down-regulation of CCR5 (a coreceptor for HIV-1 non-SI [NSI] strains), and up-regulation of CXCR4 (a coreceptor for HIV-1 SI variants). Here we show that homozygosity of a polymorphism in the IL-4 promoter region, IL-4 -589T, is correlated with increased rates of SI variant acquisition in HIV-1-infected individuals in Japan. This mutation was also shown to be associated with elevated serum IgE levels in HIV-1-infected individuals, especially in those at advanced stages of disease. In contrast, neither a triallele polymorphism in IL-10, another Th2 cytokine, nor a biallele polymorphism in the RANTES promoter affected acquisition of the SI phenotype. This finding suggested that IL-4-589T increases IL-4 production in the human body and thus accelerates the phenotypic switch of HIV-1 from NSI to SI and possibly disease progression of AIDS.
authors.affiliation: Department of Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: E E
authors.initials: EE
authors.lastname: Nakayama
authors.forename: Y
authors.initials: Y
authors.lastname: Hoshino
authors.forename: X
authors.initials: X
authors.lastname: Xin
authors.forename: H
authors.initials: H
authors.lastname: Liu
authors.forename: M
authors.initials: M
authors.lastname: Goto
authors.forename: N
authors.initials: N
authors.lastname: Watanabe
authors.forename: H
authors.initials: H
authors.lastname: Taguchi
authors.forename: A
authors.initials: A
authors.lastname: Hitani
authors.forename: A
authors.initials: A
authors.lastname: Kawana-Tachikawa
authors.forename: M
authors.initials: M
authors.lastname: Fukushima
authors.forename: K
authors.initials: K
authors.lastname: Yamada
authors.forename: W
authors.initials: W
authors.lastname: Sugiura
authors.forename: S I
authors.initials: SI
authors.lastname: Oka
authors.forename: A
authors.initials: A
authors.lastname: Ajisawa
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.forename: Y
authors.initials: Y
authors.lastname: Takebe
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: Y
authors.initials: Y
authors.lastname: Nagai
authors.forename: A
authors.initials: A
authors.lastname: Iwamoto
authors.forename: T
authors.initials: T
authors.lastname: Shioda
mesh_terms: D000483:Alleles; D001483:Base Sequence; D018946:Chemokine CCL5 / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D015726:Giant Cells / Q000473:pathology*; D015658:HIV Infections / Q000097:blood / Q000276:immunology / Q000473:pathology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*; D006239:Haplotypes / Q000235:genetics; D006467:Hemophilia A; D020010:Heterosexuality; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D016753:Interleukin-10 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics*; D007564:Japan; D008297:Male; D008969:Molecular Sequence Data; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic / Q000235:genetics*
chemical_list: D018946:Chemokine CCL5; D016753:Interleukin-10; D015847:Interleukin-4; D007073:Immunoglobulin E