9th Annual Symposium on Antiviral Drug Resistance: Targets and Mechanisms Study on HIV-1 Trafficking Selected as Top CCR Advance in HIV/AIDS for 2008 HIV Drug Resistance Program Hosts Visitors Observing BL2*/BL3 Work News Articles and Press Releases 2008 NCI-Frederick Spring Research Festival Symposium:      “Virology: From Genetic Vehicles to Human Pathogens” NCI Center of Excellence in HIV/AIDS & Cancer Virology Symposium on HIV/AIDS Research at the National Cancer Institute:      A Record of Sustained Excellence Think Tank Meeting Invited Student Symposium Eric Freed Served as Guest Editor for Special Issue of Virus Research Retroviruses Book Available Online

9th Annual Symposium on Antiviral Drug Resistance: Targets and Mechanisms The 9th Annual Symposium on Antiviral Drug Resistance: Targets and Mechanisms was held November 16-19, 2008, at the Wyndham Virginia Crossings Hotel and Conference Center in Richmond, Virginia. Sponsored by the University of Pittsburgh and co-sponsored by the HIV Drug Resistance Program, NCI, this annual meeting brings together researchers in a variety of virus systems to exchange new information on viral targets for therapy, on antiviral drugs, and on resistance to these drugs. The focus is on specific molecular targets, their normal structure and function, their interactions with antiviral drugs, and the evolutionary basis and specific mechanisms of viral resistance.  Organized by molecular target, the program includes presentations by invited speakers as well as oral and poster presentations selected from submitted abstracts. Details about the Symposium, including the program/abstract book and photos, are available at the Symposium website.   [Top of page] Study on HIV-1 Trafficking Selected as Top CCR Advance in HIV/AIDS for 2008 A study by Dr. Eric Freed and colleagues on "Real-Time Visualization of HIV-1 Gag Trafficking in Infected Macrophages" was selected as the Center for Cancer Research (CCR) Science Advance of the year in HIV/AIDS research. Featured in a recent CCR In the Journals article, Dr. Freed's study "demonstrates that HIV-1 particles are retained in internal reservoirs within host cells from which they can be rapidly released at opportune times, such as when contact is established with uninfected cells....The results of this study may set the groundwork for the development of new HIV treatments based on interruption of intracellular viral trafficking." Further details, including the original publication of the study in PLoS Pathogens, are available at the Recent HIV DRP Publications web page.   [Top of page] HIV Drug Resistance Program Hosts Visitors Observing BL2*/BL3 Work Dr. Nancy Chung (second from right) in the BL2* staging area with (from left to right) Margaret Lange, Eleftherios Michailidis, and Bruno Marchand. The HIV Drug Resistance Program hosted several members of the laboratories of Drs. Donald Burke and Stefan Sarafianos from the University of Missouri to demonstrate the BL2*/BL3 practices and protocols used in the DRP. Dr. Nancy Chung in Dr. Vineet KewalRamani's group conducted the training for the visitors, which included Dr. Burke and fellows Margaret Lange, Bruno Marchand, and Eleftherios Michailidis. In addition to demonstrating experiments using GHOST cell infections with live HIV-1, Dr. Chung demonstrated TZM cell titrations, which are commonly used by laboratories conducting research on antiviral inhibitors. Observing the BL2*/BL3 work firsthand proved very helpful to the guests; in Dr. Burke's words, "there were a thousand little details that can only be learned by watching it in action." [Top of page] News Articles and Press Releases News Articles on Recent Nature Paper by Le Grice Lab The following news articles highlight a Nature paper published in May 2008 by a collaborative team including members of the Le Grice lab (Stuart Le Grice and Jason Rausch) on their findings that the enzymatic activities of HIV reverse transcriptase are determined by its binding orientation on the substrate (to view the articles, click on the titles below): Nature News and Views feature: Molecular Biology: An HIV Secret Uncovered (PDF - 451KB) Harvard University Gazette Online feature: Research Reveals Workings of Anti-HIV Drugs CCR Connections feature: Reverse Transcriptase: When Function Follows Direction The original article by Abbondanzieri et al. describing the study (Nature 453: 184-189): Dynamic binding orientations direct activity of HIV reverse transcriptase (PDF - 546KB) News Articles on Recent PNAS Paper by Host-Virus Interaction Branch The following news articles highlight a PNAS paper published in March 2008 by a collaborative team including members of the Host-Virus Interaction Branch (Sarah Palmer, Frank Maldarelli, Ann Wiegand, John Coffin, John Mellors) on the persistence of low-level viremia for at least 7 years in HIV-infected patients on potent antiretroviral therapy (to view the articles, click on the titles below): U.S. News & World Report: HIV Can Hide in Cells for Years BBC News: HIV 'hides from drugs for years' Forbes: HIV Can Hide in Cells for Years HealthAtoZ.com: HIV Can Hide in Cells for Years The original article by Palmer et al. describing the study (Proc. Natl. Acad. Sci. USA 105: 3879-3884, 2008): Low-level viremia persists for at least 7 years in patients on suppressive antiretroviral therapy (PDF - 664KB) Center for Cancer Research "In the Journals" Feature on Recent PNAS Article by Freed Lab The following article on the Center for Cancer Research website highlights a May 2007 PNAS paper by Drs. Eric Freed and Abdul Waheed and their collaborators on a novel mechanism by which HIV circumvents the antiviral activity of amphotericin B methyl ester (AME): HIV and Drug Resistance: Hitting a Moving Target (PDF - 214KB) The original article by Waheed et al. describing the study (Proc. Natl. Acad. Sci. USA 104: 8467-8471, 2007): HIV-1 escape from the entry-inhibiting effects of a cholesterol-binding compound via cleavage of gp41 by the viral protease (PDF - 675KB) Frederick News-Post Article on Student Intern Bilguujin Dorjsuren The following front-page article features Bilguujin Dorjsuren, a student intern in the laboratory of Dr. David Derse (reprinted with permission of the Frederick News-Post and Randall Family, LLC as published on May 16, 2007): She speaks four languages, interns at NCI — and she’s only 18 Press Releases and Related Articles on Bevirimat (PA-457), a Novel HIV-1 Inhibitor The following articles announce the results of clinical trials on bevirimat (PA-157), the first-in-class HIV-1 maturation inhibitor developed by Panacos Pharmaceuticals in collaboration with a research team in the HIV Drug Resistance Program, National Cancer Institute (to view the articles, click on the titles below): May 2007 Press Release from Panacos Pharmaceuticals: Preclinical Study Finds Protease Inhibitor-Resistant HIV May Have Reduced Potential to Develop Resistance to Panacos' Bevirimat August 2006 Article in the Boston Globe: Chinese Herb May Yield Drug for AIDS June 2006 Press Release from Panacos Pharmaceuticals: Panacos Presents Data on Lack of Clinical Resistance Development to Bevirimat (PA-457) at International HIV Drug Resistance Conference June 2006 Article in Scientific American: A New Assault on HIV: The Constant Search for Weak Points in the Virus Yields Ideas for a Wholly New Class of Drug April 2006 Press Release from Panacos Pharmaceuticals: PA-457 Phase 2b Trial Design Agreed with FDA; Study Projected to Begin in Q2 2006 August 2005 Press Release from Panacos Pharmaceuticals: Panacos Drug Candidate PA-457 Shows Potent Antiviral Activity in HIV-infected Patients; Viral Load Reduction Meets Primary Endpoint of Phase 2a Study May 2005 Press Release from Panacos Pharmaceuticals: V. I. Technologies and Collaborators Present Three Studies on the Molecular Target of PA-457, First-in-Class HIV Maturation Inhibitor, at the Cold Spring Harbor Retrovirus Conference BusinessWeek online: A Better Way To Ambush AIDS?—Panacos Pharmaceuticals' experimental drug opens the door to a new line of attack To view the published results of a study elucidating the mechanism of action of PA-457, go to Proc. Natl. Acad. Sci. USA 100: 13555-13560, 2003 (PDF - 384KB). Press Release and Related Articles on the Discovery of How One Type of Cancer-Causing Virus Evades the Body's Natural Defenses The following articles describe research performed by Dr. David Derse and colleagues on the mechanism by which human T-cell leukemia virus type 1 circumvents the body's natural defenses (to view the articles, click on the titles below): February 2007 Press Release from the National Cancer Institute: NCI Scientists Discover How T-Cell Leukemia Viruses Evade Body's Defense Mechanisms Cancer Research Highlights Article in the NCI Cancer Bulletin (page 3): Study Describes How Virus Evades Body's Defenses (PDF - 434KB) Featured Article in NIH Research Matters: How T-Cell Leukemia Viruses Virus Evade the Body's Defenses The original article by Derse et al. describing the study (Proc. Natl. Acad. Sci. USA 104: 2915-2920, 2007): Resistance of human T cell leukemia virus type 1 to APOBEC3G restriction is mediated by elements in nucleocapsid (PDF - 692KB) Popular Mechanics Feature and Related Article on the RT-SHIV Animal Model of HIV Infection The following articles describe research performed by Drs. Vineet KewalRamani and Zandrea Ambrose on the RT-SHIV animal model of HIV-1 pathogenesis, persistence, and response to antiretroviral therapy (to view the articles, click on the titles below): December 2006 PopularMechanics.com World AIDS Day special on the RT-SHIV research in Dr. KewalRamani's lab: Fighting HIV by Building a New Killer The original article by Ambrose et al. describing the RT-SHIV model (J. Virol. 78: 13553-13561, 2004): In vitro characterization of a simian immunodeficiency virus-human immunodeficiency virus (HIV) chimera expressing HIV type 1 reverse transcriptase to study antiviral resistance in pigtail macaques (PDF - 207KB) NCI-Frederick Spotlight on Dr. John Coffin This interview with Dr. John Coffin was the featured article in August 2005 on the home page of the NCI-Frederick website. NCI-Frederick Spotlight on Dr. Stephen Hughes This interview with Dr. Stephen Hughes was the featured article in July 2004 on the home page of the NCI-Frederick website. in-cites -- An Interview with Dr. John M. Coffin In this December 2003 in-cites interview, Dr. Coffin discusses his highly cited Science paper, "HIV population dynamics in vivo—implications for genetic variation, pathogenesis, and therapy."

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Think Tank Meeting The HIV Drug Resistance Program (DRP) hosted the 2008 Think Tank Meeting on April 16 at the NCI-Frederick Conference Center. Covering all topics related to retrovirology, this annual event brings together investigators from NCI, NIH, and academic institutions in the Washington and Baltimore areas with research interests related to the Program's goals for a stimulating day of short presentations and discussion. Since its inception in 1998, the Think Tank Meeting has been very successful at fostering collaborations among these investigators.  The DRP has broadened participation in the Think Tank Meeting by periodically inviting senior graduate students involved in retrovirus research outside the NIH to attend the Think Tank and to participate in an informal symposium with members of the DRP the following day (see Invited Student Symposium below). 2008 Think Tank Presentations: Yossef Raviv ATP synthase beta chain is a receptor for HIV-1 transmission by DC-SIGN expressing Raji cells David Derse Quantitative comparison of HIV-1 and HTLV-1 cell-to-cell infection in a model cell culture system Maribeth Eiden Gibbon ape leukemia virus: An emerging zoonosis Sher Hendrickson Mitochondrial DNA haplogroups influence AIDS progression Kyeongeun Lee HIV-1 PR kills cycling cells Mary Kearney HIV-1 evolution in vivo Wei Zao Chen Human domain antibodies against HIV-1 as exceptionally potent cross-reactive neutralizers Jacob Estes Early host innate immune response at the portal of entry following intra-vaginal transmission Frank Maldarelli Persistent HIV-1 viremia during suppressive antiviral therapy Shixing Tang Nanoparticle based new assays for enhanced detection of HIV and other pathogens Andrew Yang Small molecule screening for reactivation of latent HIV Antonio Valentin Electroporation of optimized DNA vaccines leads to greatly enhanced responses in blood and mucosal surfaces James Thomas Possible mechanism of premature reverse transcription in NC-mutant HIV-1 Stuart Le Grice Interaction of RNase H inhibitors with RT Christie Vu Evaluation of nucleoside analogs against HIV-1 reverse transcriptase Krista Frankenberry HIV-1 RT connection domain mutations decrease RNase H cleavage and increase AZT resistance Min Li Synapsis of viral DNA ends by HIV-1 integrase Atreyi Chatterjee The chromodomain of Tf1 integrase is critical for integration and target site selection Jessica Marinello HIV-1 integrase mutations and resistance to Raltegravir and Elvitegravir Eri Miyagi Replication of Vif-deficient HIV-1 in a semi-permissive APOBEC3G expressing T cell line Xiao-Fang Yu A critical region in potent anti-viral cytidine deaminases mediates specific RNA binding and HIV-1 inhibition Anjali Joshi Functional replacement of a retroviral late domain by ubiquitin fusion David Ott Assembly properties of a nucleocapsid deletion mutant Rachael Crist Assembly properties of Gag-zipper chimeric proteins Michael Moore Match.com: The most popular "cyt" for HIV-1 gRNA to find its partner [Top of page] Invited Student Symposium In conjunction with the 2005 Think Tank Meeting, the DRP hosted the third Invited Student Symposium on April 6. After attending the Think Tank Meeting, the following senior graduate students from outside the NIH community presented short talks on their retrovirology research to the DRP staff and convened with the Program's faculty for informal discussions. Danso Ako-Adjei (Volker Vogt Laboratory, Cornell University) Jared Auclair (Celia Schiffer Laboratory, University of Massachusetts Medical School) Shardell Hawkins (Michael Summers Laboratory, Howard Hughes Medical Institute and University of Maryland Baltimore County) Shari Kaiser (Michael Emerman Laboratory, Fred Hutchinson Cancer Research Center) Juliana Leung (Stephen Goff Laboratory, Howard Hughes Medical Institute and Columbia University College of Physicians and Surgeons) Urvi Parikh (John Mellors Laboratory, University of Pittsburgh School of Medicine) David Sayah (Jeremy Luban Laboratory, Columbia University College of Physicians and Surgeons) [Top of page] Eric Freed Served as Guest Editor for Special Issue of Virus Research

The cover image was reprinted from Virus Research, Vol. 106, No. 2, Copyright 2004, with permission from Elsevier. The original source of the artwork was Proc. Natl. Acad. Sci. USA 99: 955-960, 2002 (Copyright 2002, National Academy of Sciences, U.S.A.).

Dr. Eric Freed served as guest editor for the December 2004 issue of Virus Research, which was devoted to mechanisms of enveloped virus budding. In addition to writing the preface (PDF - 33KB) to this special issue, Dr. Freed solicited chapters from leading investigators studying a range of enveloped viruses, edited the chapters, and coordinated the review process. He also contributed a chapter on retrovirus budding (Demirov and Freed, pp. 87-102, PDF - 443KB) and provided the artwork for the journal's cover, showing an electron micrograph of TSG-5' inhibiting HIV-1 budding.

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Retroviruses Book Available Online The full text of the book Retroviruses (edited by John M. Coffin, Stephen H. Hughes, and Harold E. Varmus, 1997, Cold Spring Harbor Laboratory Press) is now available online at the National Center for Biotechnology Information website. Figures, tables, and retrotrivia features from the book are also available at this website. (Permission to depict the book's cover here was kindly granted by the publisher.)

Last modified: 19 December 2008