HIV-HOST INTERACTIONS Edited by Theresa L. Chang HIV-Host Interactions Edited by Theresa L. Chang Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2011 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which permits to copy, distribute, transmit, and adapt the work in any medium, so long as the original work is properly cited. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. As for readers, this license allows users to download, copy and build upon published chapters even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. Notice Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published chapters. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. Publishing Process Manager Silvia Vlase Technical Editor Teodora Smiljanic Cover Designer Jan Hyrat Image Copyright sgame, 2011. Used under license from Shutterstock.com First published October, 2011 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechweb.org HIV-Host Interactions, Edited by Theresa L. Chang p. cm. 978-953-307-442-9 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface IX Part 1 Viral Components and Host Interactions 1 Chapter 1 Molecular Crosstalk between HIV-1 Integration and Host Proteins – Implications for Therapeutics 3 Youichi Suzuki, Yasutsugu Suzuki and Naoki Yamamoto Chapter 2 HIV Infection «HIV Tat Protein, a Key Factor in Pathogenesis and Immune System Dysregulation: Implication of IL-10» 25 Ben Haij N., Planès R., Mzoughi O. and Bahraoui E. Chapter 3 HIV-1 Nef Transfer and Intracellular Signalling in Uninfected Cells 61 Zulema A. Percario, Giorgio Mangino, Valentina Gallo, Maria Vincenza Chiantore, Gianna Fiorucci, Giovanna Romeo and Elisabetta Affabris Chapter 4 Clinical Relevance of HIV-1 Superinfection 79 Daniëlle Hoogmoed, Marion Cornelissen and Antoinette van der Kuyl Part 2 Innate Immunity 97 Chapter 5 Innate Immune Responses in HIV-Infection 99 Wilfried Posch, Cornelia Lass-Flörl and Doris Wilflingseder Chapter 6 Human Defensins in HIV Infection: Friends or Foes? 127 Rachna Shah and Theresa L. Chang VI Contents Part 3 Host Factors in HIV Pathogenesis 147 Chapter 7 Factors Contributing to HIV-1 Induced Pathogenesis in the Human Thymus 149 Bianca Blom, Marta Epeldegui and Christel H. Uittenbogaart Chapter 8 Impact of HIV Infection and HAART Therapy on CD4 T Helper Cell Subset Expression and Function 183 Christina Guzzo, Nor Fazila Che Mat, Xiubo Zhang and Katrina Gee Chapter 9 Genetic Factors that Influence HIV Infection: The Role of the Major Histocompatibility Complex System 205 Daniel Pérez-Núñez and Narcisa Martínez-Quiles Chapter 10 Interactions of Infectious HIV-1 Virions with Erythrocytes: Implications for HIV-1 Pathogenesis and Infectivity 239 Zoltan Beck and Carl R Alving Part 4 Co-Infection 255 Chapter 11 In Vitro and In Vivo Transactivation of HIV-1 by Human Herpesvirus 6 257 Ongrádi Joseph, Kövesdi Valéria, Nagy Károly, Matteoli Barbara, Ceccherini-Nelli Luca and Ablashi Dharam Chapter 12 Inducing Immune Protection Against Trichomonas vaginalis: A Novel Vaccine Approach to Prevent HIV Transmission 299 Sarah Cudmore, Jeffrey Smith and Gary Garber Part 5 Animal Model 323 Chapter 13 Macaque-Tropic HIV-1 Derivatives: A Novel Experimental Approach to Understand Viral Replication and Evolution in Vivo 325 Masako Nomaguchi, Naoya Doi, Sachi Fujiwara and Akio Adachi Chapter 14 The Quest for a Small Animal Model for HIV Infection and Disease 349 Jorge C.G. Blanco, Lioubov M. Pletneva, Lorraine E. Earle and William I. Frels Preface It has been 30 years since the first case of acquired immunodeficiency syndrome (AIDS) was reported. Worldwide, there are approximately 33 million people currently living with HIV, and 2.6 million became newly infected in 2009 (UNAIDS 2010). In the United States, an estimated 56,000 people become newly infected with HIV every year, and this number has remained stable. Importantly, more than 21% of the 1.1 million infected individuals in the United States are unaware of their infection. While significant scientific progress in HIV infection has been made, especially the development of antiretroviral therapy that prolongs the lives of HIV-infected individuals and appears to be a promising strategy for HIV prevention, HIV remains one of the major global health threats. Currently, there is no vaccine to prevent HIV infection nor is there a cure for HIV/AIDS. Louis Pasteur said, “In the fields of observation, chance favors only the prepared mind.” We may overcome the challenges of HIV/AIDS in the future if we continue to increase our knowledge of HIV infection. The chapters comprising this book focus on various aspects of HIV and host interactions. Suzuki and colleagues review the molecular interaction between HIV integrase and cellular factors, and highlight potential drug designs. The chapter from Dr. Bahraoui’s group focuses on the mechanism of HIV Tat protein-mediated IL-10 induction and the impact of Tat on HIV pathogenesis. Percario and colleagues provide a clear view of HIV Nef functions in vitro. Hoogmoed et al. review HIV superinfection and its clinical outcome. Posch and colleagues focus on the interplay between HIV and innate immune responses including complement and immune cells, especially dendritic cells. Shah and Chang summarize the Janus-like role of innate effectors such as defensins in HIV infection. A comprehensive review of host factors that contribute to HIV pathogenesis is provided by Uittenbogaart’s team. Guzzo and colleagues review the interplay between T cell subsets and HIV infection. Nuñez and Martinez- Quiles discuss the role of the MHC in HIV infection. The chapter from Beck and Alving focuses on the role of erythrocytes in HIV pathogenesis. Two chapters examine the role of co-infection: Ongrádi’s team discusses the impact of human herpesvirus 6 on HIV in vitro and in vivo, and Garber’s team addresses the effect of Trichomonas vaginalis on HIV transmission. As the limited number of suitable animal models continues to impede progress toward understanding HIV transmission and pathogenesis, two chapters discuss strategies for studying HIV in animal models. Nomaguchi’s team focuses on generation of HIV molecular clones that can be used in X Preface macaques. Blanco and colleagues summarize the potential use of cotton rats for studying HIV infection. This book is one of the HIV infection series published by InTech-Open Access Publisher. Other aspects in HIV infection absent in this book may be covered in other books. It was my pleasure to serve as the Ad Hoc Editor of this book and to read the manuscripts of these chapters. I thank all contributors for their efforts and hope that this book will provide insights into development of new strategies of HIV prevention and treatment. September 2011 Dr. Theresa L. Chang Public Health Research Institute and Department of Microbiology and Molecular Genetics, University of Medicine and Dentistry of New Jersey - New Jersey Medical School United States [...]... protein-protein interactions (PPIs) could also serve as attractive targets of drugs for human 4 HIV-Host Interactions therapeutics (Cochran, 2001; Arkin & Wells, 2004; Pagliaro et al., 2004; Ryan & Matthews, 2005) PPIs are central to most biological processes including virus infection and many human diseases are attributed to aberrant PPIs in cells Not surprisingly, there are a number of interactions. .. cells, Huwe1 may act as a scaffolding modulator that reduces infectivity of virions by interfering with the proper localization (left) or function (right) of HIV-1 GagPol precursor through interactions with IN 16 HIV-Host Interactions Another possible mechanism for the Huwe1-mediated negative modulation of HIV-1 infectivity is that Huwe1 could mask the IN region of Gag-Pol, thereby blocking the incorporation... particles independently of the Gag/Pol precursor protein EMBO J., Vol 16, No 16, pp 5113-5122 24 HIV-Host Interactions Wu, X.; Liu, H.; Xiao, H.; Conway, J.A.; Hehl, E.; Kalpana, G.V.; Prasad, V.; Kappes, J.C (1999) Human immunodeficiency virus type 1 integrase protein promotes reverse transcription through specific interactions with the nucleoprotein reverse transcription complex J Virol., Vol 73, No 3,... interacting with HIV-1 IN Although the enzymatic activities of HIV-1 IN in the integration reaction have been clearly defined by in vitro biochemical studies, numerous genetic analysis of HIV-1 DNA have 8 HIV-Host Interactions demonstrated that mutations in the IN gene, including deletion mutants, influence many other stages of viral replication in addition to integration This pleiotropic effect of IN is characterized... several functional domains (Fig 3A) (Engelman & Cherepanov, 2008) The N-terminal 92 amino acid region is termed the PWWP (Pro-Trp-Trp-Pro) domain The PWWP domain is conserved amongst the HRP family 10 HIV-Host Interactions proteins and is thought to function as a protein-protein interaction domain and/or DNAbinding domain (Stec et al., 2000; Qiu et al., 2002) LEDGF also includes three segments of polar... infection (Cereseto et al., 2005) A recent study from the same group showed that another HAT, GCN5, was also able to mediate the acetylation of HIV-1 IN, and provirus formation was inefficient in GCN5- 12 HIV-Host Interactions depleted cells (Terreni et al., 2010) However, it should be noted that the role of acetylation of IN in HIV-1 replication remains controversial (Topper et al., 2007; Vandegraaff & Engelman,... retroviral research Further experiments will be therefore required to unveil the role of IN and its cellular cofactors in the active transport of the HIV-1 PIC into the nucleus (Suzuki & Craigie 2007) 14 HIV-Host Interactions 4.4 Cellular interactors affecting on postintegration steps Following integration, the provirus serves as a template for viral gene expression During this postintegration process, disassembly... persons Thus, understanding the molecular basis of virus-host interactions should provide new insights into alternative strategies for the treatment of HIV infection and AIDS In this chapter, we focus our attention on integration, an essential step in the HIV replication cycle catalyzed by IN, and review the current knowledge of molecular interactions between IN and cellular cofactors 2 HIV infection... J Biol Chem., Vol 278, No 1, pp 372-381 Cherepanov, P.; Devroe, E.; Silver, P.A.; Engelman, A (2004) Identification of an evolutionarily conserved domain in human lens epithelium-derived growth 18 HIV-Host Interactions factor/transcriptional co-activator p75 (LEDGF/p75) that binds HIV-1 integrase J Biol Chem., Vol 279, No 47, pp 48883-48892 Cherepanov, P.; Ambrosio, A.L.; Rahman, S.; Ellenberger, T.;... 4 Jacks, T.; Power, M.D.; Masiarz, F.R.; Luciw, P.A.; Barr, P.J.; Varmus, H.E (1988) Characterization of ribosomal frameshifting in HIV-1 gag-pol expression Nature, Vol 331, No 6153, pp 280-283 20 HIV-Host Interactions Kalpana, G.V.; Marmon, S.; Wang, W.; Crabtree, G.R.; Goff, S.P (1994) Binding and stimulation of HIV-1 integrase by a human homolog of yeast transcription factor SNF5 Science, Vol 266, . HIV-HOST INTERACTIONS Edited by Theresa L. Chang HIV-Host Interactions Edited by Theresa L. Chang Published. becoming increasingly clear that protein-protein interactions (PPIs) could also serve as attractive targets of drugs for human HIV-Host Interactions 4 therapeutics (Cochran, 2001; Arkin. www.intechopen.com Additional hard copies can be obtained from orders@intechweb.org HIV-Host Interactions, Edited by Theresa L. Chang p. cm. 978-953-307-442-9 free online editions