An Horizon, a Porthole, and a New Book

Janine Selendy is what one might call an “accidental altruist.” Early in her teen years, she came face-to-face with the astonishingly poor living conditions faced by people living in Iran. This pivotal experience led Selendy away from her intended career in diplomacy and into a very busy life aimed at changing people’s lives at the level of their basic needs.

Selendy initially set out to become a doctor, and she soon began to participate in environmental health work such as the cleanup of PCBs in the Hudson river. However, the more she interacted with scientific literature, the more frustrated she became that the literature seemed filled only with negatives and problems, yet rarely addressed solutions or emphasized what was already being done about these problems.

To fill this gap, Selendy founded Horizon International, a non-profit organization based at Yale University which addresses health, environmental and poverty issues. In an era before the internet, Selendy also capitalized on the power of television to enlighten and inform a wider audience on these important issues, and to date she and her team have produced over twenty documentaries.

Next, Selendy and the leaders of Horizon International also sought and received funding from the National Science Foundation to create a program that would provide educational games and multimedia for young people. They named this website “Magic Porthole” because, “if you come in here, you don’t know what you’re going to find next!”

Amidst all of this activity, Selendy has also managed to find the time to edit a book, Water and Sanitation Related Diseases and the Environment: Challenges, Interventions and Preventive Measures, which will be published by Wiley next month (July 2011). The book chapters are authored by an array of high-profile scientists and public health leaders and cover topics that range from “water and war” to “diarrhea and nutrition.”

Selendy discusses her history, work, and aspirations in live interview hosted on the website Listen and download the MP3 here.

Read a more detailed biography of Selendy here.

Find out more about Selendy’s book here.

Stopping HIV in the Macrophage

HIV is an elusive virus. Affecting more than 30 million people worldwide, the virus thrives in the human immune system by adapting in a number of ways, which makes effective treatments and an eventual cure exceedingly difficult. However, scientists at the University of Rochester and Emory University recently unveiled one of the mechanisms by which HIV is able to replicate itself inside the human immune system: dNTP substitution in macrophages.1 With this discovery, it is possible that new treatments are on the horizon.

HIV drugs typically target helper T Cells (CD4+ T cells)—the white blood cells that are eventually depleted by the virus. However, HIV also infects macrophages2—a derivative of monocytes—but until recently, scientists were unable to determine how the virus was able to thrive inside this kind of cell.

To replicate, HIV ordinarily uses the host’s own protein machinery—specifically the nucleoside dNTP (deoxynucleoside triphosphate), which is broken down to become a building block for DNA and RNA. However, dNTP is absent in macrophages, because macrophages don’t replicate. In lieu of dNTP, researchers Baek Kim and Raymond Schinazi found that the virus recruits a closely related molecule, rNTP (ribonucleoside triphosphate), to replicate. Kim and Schinazi then confirmed their findings by showing that when they blocked the ability of the virus to interact with rNTP, they reduced HIV’s ability to replicate in macrophages by more than 90%.

The ability to thwart HIV reproduction in macrophages could be a more effective than existing treatments at limiting the ravages of the virus for several reasons:

  1. Macrophages appear to be the first cells infected by HIV.
  2. Once helper T cells become depleted, macrophages may serve as the source of HIV production.
  3. Infected macrophages eventually spreads HIV to the central nervous system.

Some drugs that are already being tested for other purposes also happen to offer rNTP-targeting potential. Cordycepin, a compound derived from wild mushrooms, is one such drug; currently it is being tested as an anti-cancer drug, but it has also been shown to efficiently inhibit HIV-1 replication in macrophages.

Resources from Wiley on This Topic
Antiviral Drugs: From Basic Discovery Through Clinical Trials

by Wieslaw M. Kazmierski

HIV-1 Integrase: Mechanism and Inhibitor Design

by Nouri Neamati, Binghe Wang

AIDS and Tuberculosis: A Deadly Liaison

by Stefan H. E. Kaufmann and Bruce D. Walker

1. Kennedy EM, Gavegnano C, Nguyen L, Slater R, Lucas A, Fromentin E, Schinazi RF, & Kim B (2010). Ribonucleoside triphosphates as substrate of human immunodeficiency virus type 1 reverse transcriptase in human macrophages. The Journal of biological chemistry, 285 (50), 39380-91 PMID: 20924117

2. Benaroch, P., Billard, E., Gaudin, R., Schindler, M., & Jouve, M. (2010). HIV-1 assembly in macrophages Retrovirology, 7 (1) DOI: 10.1186/1742-4690-7-29