title: CXCR4-tropic, but not CCR5-tropic, human immunodeficiency virus infection is inhibited by the lipid raft-associated factors, acyclic retinoid analogs, and cholera toxin B subunit.
abstract: Development of an effective low-cost anti-acquired immunodeficiency syndrome (AIDS) drugs is needed for treatment of AIDS patients in developing countries. Host cell lipid raft microdomains, which are enriched with cholesterol, glycolipids, ceramide, and gangliosides, are important for human immunodeficiency virus type 1 (HIV-1) entry. Retinoid analogs have been shown to modulate ceramide levels in the cell membrane, while cholera toxin B subunit (CT-B) specifically binds to the ganglioside GM1. In this study, we found that the acyclic retinoid analogs geranylgeranoic acid (GGA) and NIK-333 as well as CT-B efficiently attenuate CXCR4-tropic, but not CCR5-tropic, HIV-1 vector infection. We also found that GGA and NIK-333 suppress CXCR4-tropic HIV-1 infection by attenuating CXCR4 expression. CT-B also attenuated CXCR4-tropic HIV-1 infection, but did not suppress CXCR4 expression. These results suggest a distinct role for lipid raft microdomains in CXCR4- and CCR5-tropic HIV-1 infections and illuminate novel agents for the development of AIDS therapy.
authors: Division of Cytokine Signaling, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan.
authors: Haruka
authors: H
authors: Kamiyama
authors: Katsura
authors: K
authors: Kakoki
authors: Sayuri
authors: S
authors: Shigematsu
authors: Mai
authors: M
authors: Izumida
authors: Yuka
authors: Y
authors: Yashima
authors: Yuetsu
authors: Y
authors: Tanaka
authors: Hideki
authors: H
authors: Hayashi
authors: Toshifumi
authors: T
authors: Matsuyama
authors: Hironori
authors: H
authors: Sato
authors: Naoki
authors: N
authors: Yamamoto
authors: Tetsuro
authors: T
authors: Sano
authors: Yoshihiro
authors: Y
authors: Shidoji
authors: Yoshinao
authors: Y
authors: Kubo
mesh_terms: D019380:Anti-HIV Agents / Q000378:metabolism*; D002772:Cholera Toxin / Q000378:metabolism*; D004224:Diterpenes / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D019718:Receptors, CXCR4 / Q000378:metabolism*; D015728:Receptors, HIV / Q000378:metabolism; D012176:Retinoids / Q000378:metabolism; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000378:metabolism; D056189:Viral Tropism; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; C527276:CXCR4 protein, human; D004224:Diterpenes; D019718:Receptors, CXCR4; D015728:Receptors, HIV; D012176:Retinoids; C487689:(2E,4E,6E,10E)-3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid; D014212:Tretinoin; C034534:3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid; C040155:geranylgeranic acid; D002772:Cholera Toxin