Polymorphism in the interleukin-4 promoter affects acquisition of human immunodeficiency virus type 1 syncytium-inducing phenotype.
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.
Nakayama
E E
EE
Department of Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Hoshino
Y
Y
Xin
X
X
Liu
H
H
Goto
M
M
Watanabe
N
N
Taguchi
H
H
Hitani
A
A
Kawana-Tachikawa
A
A
Fukushima
M
M
Yamada
K
K
Sugiura
W
W
Oka
S I
SI
Ajisawa
A
A
Sato
H
H
Takebe
Y
Y
Nakamura
T
T
Nagai
Y
Y
Iwamoto
A
A
Shioda
T
T
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*
D018946:Chemokine CCL5; D016753:Interleukin-10; D015847:Interleukin-4; D007073:Immunoglobulin E