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Host-Pathogen Interactions of Retroviruses Molecular Biology International Host-Pathogen Interactions of Retroviruses Guest Editors: Abdul A. Waheed, Abraham L. Brass, Suryaram Gummuluru, and Gilda Tachedjian Host-Pathogen Interactions of Retroviruses Molecular Biology International Host-Pathogen Interactions of Retroviruses Guest Editors: Abdul A. Waheed, Abraham L. Brass, Suryaram Gummuluru, and Gilda Tachedjian Copyright © 2012 Hindawi Publishing Corporation. All rights reserved. This is a special issue published in “Molecular Biology International.” All articles are open access articles distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Editorial Board Sherif Abou Elela, Canada Duane L. Guernsey, Canada Cecilia Saccone, Italy Mamoun Ahram, Jordan Mark J. Guiltinan, USA Sharad S. Singhal, USA Yogesh C. Awasthi, USA Abdelali Hannoufa, Canada Mouldy Sioud, Norway Melissa Brown, Australia Michael Kessel, Germany Surjit Kaila Srai, UK WilliamJ.Brown,USA Andrzej Kloczkowski, USA E. E. Strehler, USA George A. Calin, USA Tomasz Kordula, USA Malayannan B. Subramaniam, USA R. Holland Cheng, USA Van Luu-The, Canada Jozsef´ Szeberenyi,´ Hungary Donato Civitareale, Italy William F. Marzluff,USA Jamboor Vishwanatha, USA Denis I. Crane, Australia Dimitrios Morikis, USA Virginia K. Walker, Canada Alessandro Desideri, Italy Ishita Mukerji, USA Christoph Winkler, Singapore George Dickson, UK Zafar Nawaz, USA Wolfgang Wintermeyer, Germany Sandra J. Gendler, USA Bill Pohajdak, Canada Zendra E. Zehner, USA D. C. Gowda, USA A. L. N. Rao, USA Wolfgang F. Graier, Austria Joseph Rothnagel, Australia Contents Host-Pathogen Interactions of Retroviruses, Abdul A. Waheed, Abraham L. Brass, Suryaram Gummuluru, and Gilda Tachedjian Volume 2012, Article ID 648512, 4 pages Cellular Cofactors of Lentiviral Integrase: From Target Validation to Drug Discovery,OliverTaltynov, Belete A. Desimmie, Jonas Demeulemeester, Frauke Christ, and Zeger Debyser Volume 2012, Article ID 863405, 16 pages Protease-Mediated Maturation of HIV: Inhibitors of Protease and the Maturation Process, Catherine S. Adamson Volume 2012, Article ID 604261, 13 pages The Role of TNPO3 in HIV-1 Replication, Felipe Diaz-Griffero Volume 2012, Article ID 868597, 6 pages Factors Important to the Prioritization and Development of Successful Topical Microbicides for HIV-1, Karen W. Buckheit and Robert W. Buckheit Jr. Volume 2012, Article ID 781305, 12 pages The Continuing Evolution of HIV-1 Therapy: Identification and Development of Novel Antiretroviral Agents Targeting Viral and Cellular Targets, Tracy L. Hartman and Robert W. Buckheit Jr. Volume 2012, Article ID 401965, 17 pages Dynamic Association between HIV-1 Gag and Membrane Domains, Ian B. Hogue, G. Nicholas Llewellyn, and Akira Ono Volume 2012, Article ID 979765, 13 pages Retroviral Env Glycoprotein Trafficking and Incorporation into Virions,TsutomuMurakami Volume 2012, Article ID 682850, 11 pages Restriction of Retroviral Replication by Tetherin/BST-2, Jason Hammonds, Jaang-Jiun Wang, and Paul Spearman Volume 2012, Article ID 424768, 9 pages The Impact of Macrophage Nucleotide Pools on HIV-1 Reverse Transcription, Viral Replication, and the Development of Novel Antiviral Agents, Christina Gavegnano, Edward M. Kennedy, Baek Kim, and Raymond F. Schinazi Volume 2012, Article ID 625983, 8 pages The Impact of HIV Genetic Polymorphisms and Subtype Differences on the Occurrence of Resistance to Antiretroviral Drugs, Mark A. Wainberg and Bluma G. Brenner Volume 2012, Article ID 256982, 10 pages HIV-1 Reverse Transcriptase Still Remains a New Drug Target: Structure, Function, Classical Inhibitors, and New Inhibitors with Innovative Mechanisms of Actions, Francesca Esposito, Angela Corona, and Enzo Tramontano Volume 2012, Article ID 586401, 23 pages HIV Assembly and Budding: Ca2+ Signaling and Non-ESCRT Proteins Set the Stage, Lorna S. Ehrlich and Carol A. Carter Volume 2012, Article ID 851670, 12 pages APOBEC3 versus Retroviruses, Immunity versus Invasion: Clash of the Titans,AnnM.Sheehyand Julie Erthal Volume 2012, Article ID 974924, 11 pages Mechanisms of HIV Transcriptional Regulation and Their Contribution to Latency, Gillian M. Schiralli Lester and Andrew J. Henderson Volume 2012, Article ID 614120, 11 pages TRIM5 and the Regulation of HIV-1 Infectivity, Jeremy Luban Volume 2012, Article ID 426840, 6 pages Probing Retroviral and Retrotransposon Genome Structures: The “SHAPE” of Things to Come, Joanna Sztuba-Solinska and Stuart F. J. Le Grice Volume 2012, Article ID 530754, 12 pages TRIM22: A Diverse and Dynamic Antiviral Protein, Clayton J. Hattlmann, Jenna N. Kelly, and Stephen D. Barr Volume 2012, Article ID 153415, 10 pages Hindawi Publishing Corporation Molecular Biology International Volume 2012, Article ID 648512, 4 pages doi:10.1155/2012/648512 Editorial Host-Pathogen Interactions of Retroviruses Abdul A. Waheed,1 AbrahamL.Brass,2 Suryaram Gummuluru,3 and Gilda Tachedjian4, 5, 6 1 Virus-Cell Interaction Section, HIV Drug Resistance Program, National Cancer Institute at Frederick, Frederick, MD 21702, USA 2 Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655, USA 3 Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA 4 Center for Virology, Burnet Institute, Melbourne, VIC 3004, Australia 5 Department of Microbiology, Monash University, Clayton, VIC 3168, Australia 6 Department of Medicine, Monash University, Melbourne, VIC 3004, Australia Correspondence should be addressed to Abdul A. Waheed, [email protected] Received 30 August 2012; Accepted 30 August 2012 Copyright © 2012 Abdul A. Waheed et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Retroviruses, such as HIV-1, are enveloped RNA viruses the sexual transmission of HIV in a clinical trial setting that use the enzyme reverse transcriptase (RT) to make presents potential concern because antiretrovirals or drugs a DNA copy of their RNA genome during replication in with similar resistance profiles are used both for therapy the host cell. The retrovirus life cycle is generally divided and prevention [11]. This, in a PrEP setting, could either into two distinct phases: the early and late phase. The early result in the transmission of drug-resistant viral strains or phase encompasses virion entry into the host cell, reverse the generation of such viral strains in individuals taking transcription of the viral RNA, nuclear import of the pre- PrEP unaware of their HIV infection status, thereby limiting integration complex (PIC), and integration of viral DNA into future therapeutic options. Such concerns warrant efforts to the host chromosome. The late phase involves transcription identify novel inhibitors of HIV. Understanding the role of of viral DNA to multiple copies of viral RNA, translation host proteins in viral replication could potentially lead to of viral proteins, trafficking of viral proteins and genome the development of new therapeutic strategies to combat this to assembly sites, budding of viral particles, and, finally, deadly pathogen. maturation. A number of host factors have been implicated This special issue brings together 17 reviews by experts in specific steps of virus replication, and identification of on various aspects of the HIV-1 life cycle, highlighting the such factors is a rapidly growing field. Recently, many host significant roles played by host factors in virus replication, proteins were identified in genome-wide siRNA screens as and the antiviral agents that act on the viral and cellular being required for HIV-1 replication [1–3]. targets. These reviews do not necessarily represent an Over 25 antiretroviral drugs are currently in clinical use exhaustive inventory of the current state of research or for treating HIV-1, and except for the fusion inhibitor that opinion in the field. Instead, the reviews cover the widely targets the viral envelope glycoprotein gp41 or the coreceptor studied host-factors in each step of the HIV-1 replication CCR5, these drugs target the activity of the viral enzymes cycle and antiviral therapy targeting viable cellular and viral RT, integrase (IN), and protease (PR) [4–8]. The advent of targets. We, the guest editors, would like to sincerely thank highly active antiretroviral therapy (HAART) has made a all the authors for their contribution to this special issue and significant impact on the natural history of HIV/AIDS by the reviewers for their time and expertise. dramatically prolonging the life of HIV-infected individuals In his review “TRIM5 and the regulation of HIV-1 [9]. However, besides long-term drug toxicity and drug- infectivity,” Jeremy Luban offers an in-depth analysis of drug interactions leading to treatment failures, significant how TRIM5 impedes retroviral infection, including the limitations of antiviral therapy include the emergence of recent exciting data concerning TRIM5’s innate immune drug-resistant viral variants [10]. Further, the success of top- signaling capacity that permits the host factor to recognize ical and oral preexposure prophylaxis (PrEP) in preventing HIV-1’s capsid (CA) lattice and subsequently signal to 2 Molecular Biology International downstream antiviral effectors. This review also presents The growing field of HIV-1 nuclear import is also covered, a comprehensive
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