2006 Fiscal Year Final Research Report Summary
Mechanisms of the control of chromosome 22 gene expression associated with HIV-1-exposed but uninfected status
| Project/Area Number |
17390137
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Virology
|
|---|
| Research Institution | Kinki University |
|---|
Principal Investigator |
MIYAZAWA Masaaki Kinki University, School of Medicine, Professor, 医学部, 教授 (60167757)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KAWAHARA Sachiyo (TSUJI Sachiyo) Kinki University, School of Medicine, Associate Professor, 医学部, 講師 (60297629)
KANARI Yasuyoshi Kinki University, School of Medicine, Assistant Professor, 医学部, 助手 (60351590)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Keywords | HIV-1 / Exposed seronegative / virus-neutralizing antibody / immune resistance / APOBEC3 / chromosome 22 / gene expression / polymorphism |
|---|
| Research Abstract |
Despite multiple and repeated exposures to HIV-1, some individuals possess no detectable HIV genome and show T-cell memory responses to the viral antigens. HIV-1-reactive mucosal IgA detected in such uninfected individuals suggests their possible immune resistance against HIV acquisition. However, attempts to associate the above HIV-1-exposed but uninfected status with known resistance factors, including the CCR5A32 mutation, have been unsuccessful. Based on the mapping in chromosome 15 of a gene controlling the production of virus-neutralizing antibodies in a mouse model of retrovirus infection, we have reported a strong association between genotypes at marker loci within the syntenic chromosome 22q13.1 region and a putative dominant locus conferring strong anti-HIV-1 immune responses. In this project, we have compared expression levels of all the genes located within the above chromosomal segment utilizing DNA microarrays, and have revealed a higher induction of two particular genes
… More
in HIV antigen-stimulated peripheral blood mononuclear cells only among the exposed but uninfected, but not in the HIV-infected, individuals. Further, extensive genotyping of single nucleotide polymorphisms (SNPs) and genomic sequencing of the exposed but uninfected and HIV-infected individuals have indicated 1) a significant accumulation of a particular genotype at multiple and mutually linked SNP loci surrounding the above highly induced genes, 2) strong linkage disequilibrium between SNP genotypes across the above two gene loci observed only among the exposed but uninfected individuals, and 3) the presence of possibly functional genetic changes in the putative enhancer element located between the above two genes. Further, the expression of the DNA mutater APOBEC3G genes, whose locus is located in the chromosome 22 in close linkage with the above 22q13.1 segment, was significantly higher among the exposed but uninfected than in HIV-1-infected individuals, and its expression became much higher in CD14^+ monocytes than in other cell-types after the stimulation with interferon-α. Thus, genetically determined resistance against HIV-1 acquisition observed in the HIV-1-exposed but uninfected individuals may be explained, at least partially, by the above observed higher induction of chromosome 22 genes including APOBEC3G. Less
|
Research Products
(17 results)
-
-
-
-
[Journal Article] Vaccine-based long-term stable control of simian-human immunodeficiency virus 89.6PD replication in rhesus macaques.2007
Author(s)
Yamamoto, H., M.Kawada, T.Tsukamoto, A.Takeda, H.Igarashi, M.Miyazawa, T.Naruse, M.Yasunami, A.Kimura, T.Matano.
-
Journal Title
J. Gen. Virol. 88
Pages: 652-659
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Reference strand-mediated conformation analysis (RSCA)-based typing of multiple alleles in the rhesus macaque MHC class I Mamu-A and Mamu-B loci.2007
Author(s)
Tanaka-Takahashi, Y., M.Yasunami, T.Naruse, K.Hinohara, T.Matano, K.Mori, M.Miyazawa, M.Honda, Y.Yasutomi, Y.Nagai, A.Kimura.
-
Journal Title
Electrophoresis ([Epub ahead of print])
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Mazzotta, M. Miyazawa and M. Clerici. APOBEC3G : A possible role in resistance of HIV-exposed seronegative individuals.2007
Author(s)
Biasin, M., L.Piacentini, S.Lo Caputo, Y.Kanari, G Magri, D.Trabattoni, V.Naddeo, L.Lopalco, A.Clivio, E.Cesana, F.Fasano, C.Bergamaschi, F.
-
Journal Title
J. Infec. Dis. (in press)
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
[Journal Article] Peptide-induced immune protection of CD8^+ T cell-deficient mice against Friend retrovirus-induced disease.2006
Author(s)
Kawabata, H., A.Niwa, S.Tsuji-Kawahara, H.Uenishi, N.Iwanami, H.Matsukuma, H.Abe, N.Tabata, H.Matsumura, M.Miyazawa.
-
Journal Title
Int.Immunol. 18
Pages: 183-198
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] MHC class I-like MILL molecules are β2-microglobulin-associated, GPI-anchored glycoproteins that do not require TAP for cell surface expression.2006
Author(s)
Kajikawa, M., T.Baba, U.Tomaru, Y.Watanabe, S.Koganei, S.Tsuji-Kawahara, N.Matsumoto, K.Yamamoto, M.Miyazawa, K.Maenaka, A.Ishizu, M.Kasahara.
-
Journal Title
J.Immunol. 177
Pages: 3108-3115
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Increased liver temperature efficiently augments human cellular immune response : T cell activation and possible monocyte translocation.2006
Author(s)
Kida, Y., S.Tsuji-Kawahara, V.Ostapenko, S.Kinoshita, E.Kajiwara, H.Kawabata, T.Yuasa, I.Nishide, S.Yukawa, M.Ichinose, M.Miyazawa.
-
Journal Title
Cancer Immunol. Immunother. 55
Pages: 1459-1469
Description
「研究成果報告書概要(欧文)」より
-
-
-
[Journal Article] Genotypes at chromosome 22q12-13 are associated with HIV-1-exposed but uninfected status in Italians.2005
Author(s)
Kanari, Y., M.Clerici, H.Abe, H.Kawabata, D.Trabattoni, S.Lo Caputo, F.Mazzotta, H.Fujisawa, A.Niwa, C.Ishihara, Y.A.Takei, M.Miyazawa.
-
Journal Title
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Influence of glycosylation on the efficacy of an Env-based vaccine against SIV_<mac>239 in a macaque AIDS model.2005
Author(s)
Mori, K., C.Sugimoto, S.Ohgimoto, E.E.Nakayama, T.Shioda, S.Kusagawa, Y.Takebe, M.Kano, T.Matano, T.Yuasa, D.Kitaguchi, M.Miyazawa, Y.Takahashi, M.Yasunami, A.Kimura, N.Yamamoto, Y.Suzuki, Y.Nagai.
-
Journal Title
J. Virol. 79
Pages: 10386-10396
Description
「研究成果報告書概要(欧文)」より
-
[Patent(Industrial Property Rights)] Resistance Genes2005
Inventor(s)
宮澤正顯, Mario Clerici, 入江新司
Industrial Property Rights Holder
大阪産業振興機構, 凸版印刷(株), Immuno Clin, Ltd.
Industrial Property Number
International Patent Application No. PCT/GB2005/005078
Filing Date
2005-12-24
Description
「研究成果報告書概要(和文)」より
