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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.
AuthorsHaruka Kamiyama, Katsura Kakoki, Sayuri Shigematsu, Mai Izumida, Yuka Yashima, Yuetsu Tanaka, Hideki Hayashi, Toshifumi Matsuyama, Hironori Sato, Naoki Yamamoto, Tetsuro Sano, Yoshihiro Shidoji, Yoshinao Kubo
JournalAIDS research and human retroviruses (AIDS Res Hum Retroviruses) Vol. 29 Issue 2 Pg. 279-88 (Feb 2013) ISSN: 1931-8405 [Electronic] United States
PMID22845664 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-HIV Agents
  • CXCR4 protein, human
  • Diterpenes
  • Receptors, CXCR4
  • Receptors, HIV
  • Retinoids
  • (2E,4E,6E,10E)-3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid
  • Tretinoin
  • 3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid
  • geranylgeranic acid
  • Cholera Toxin
Topics
  • Anti-HIV Agents (metabolism)
  • Cholera Toxin (metabolism)
  • Diterpenes (metabolism)
  • HIV-1 (drug effects, physiology)
  • Humans
  • Receptors, CXCR4 (metabolism)
  • Receptors, HIV (metabolism)
  • Retinoids (metabolism)
  • Tretinoin (analogs & derivatives, metabolism)
  • Viral Tropism
  • Virus Internalization (drug effects)

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