Table of Contents

Viewpoints

• • Dzung H. Nguyen and
  • Dennis D. Taub

  Targeting Lipids to Prevent HIV Infection

  Mol Interv December 2004 4:318-320; doi:10.1124/mi4.6.3
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  Combination drug therapies exist that combat HIV replication and the production of virions. But just as the easiest way to deal with an interloper is to keep him from entering your home rather than removing him after the fact, most studies directed at reducing HIV infection are designed to keep HIV at bay, outside the host cell. Work on keeping HIV out has progressed from early work on CD4 to the chemokine receptors CCR5 and CXCR4 found on the surface of host cells. More recently, the depletion of cholesterol, the presence of which is essential for HIV entry, has been studied as a means to subvert HIV entry, and new work by Finnegan and others suggest that another useful strategy may involve increasing the amount of the sphingolipid ceramide found in lipid rafts on the surface of host cells. Increased ceramide might inhibit HIV entry by a number of means, including the displacement of cholesterol and modifying the overall organization and structure of the lipid rafts.

• • Chris Hague,
  • Randy A. Hall,
  • and Kenneth P. Minneman

  Olfactory Receptor Localization and Function: An Emerging Role for GPCR Heterodimerization

  Mol Interv December 2004 4:321-322; doi:10.1124/mi.4.6.4
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  Research on olfaction has been fraught with considerable frustration because none of the hundreds of olfactory receptors make it to the cell surface on their own when expressed in heterologous systems. Recent work indicates that the heterodimerization of olfactory receptors with β₂-adrenergic receptors results in surface expression of these G protein–coupled receptors. Similar conclusions—that heterodimerization is essential for surface expression of olfactory receptors—have been drawn from research in Drosophila utilizing completely different knockout and functional approaches. Together these findings may unlock the solution to a problem that has plagued the molecular study of olfaction since the cloning of the first olfactory G protein–coupled receptor over twelve years ago.

• • Gergely Szakács and
  • Michael M. Gottesman

  Comparing Solid Tumors with Cell Lines: Implications for Identifying Drug Resistance Genes in Cancer

  Mol Interv December 2004 4:323-325; doi:10.1124/mi.4.6.5
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  Gene expression arrays allow researchers to profile the differences between cell lines or tissues and they may identify genetic markers of development, organ maturation, or tumor progression. Although a primary tumor that grows in a host and a tumor-cell-line derived from that primary tumor and grown in vitro share similar gene expression profiles, there are, not unexpectedly, some important differences. In fact, Stein and colleagues have found that genes that are differentially expressed in primary tumors as compared to the specific genes expressed in their cell-line derivatives are more reliably predictive of tumor tractability. Thus, sensitivity in vitro might not reflect sensitivity in vivo. Because anti-tumor compounds are largely evaluated in cell culture assays, these compounds' therapeutic utility must be judged in light of genes described by Stein et al. that better predict tractability.