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1. The Role of Chemokine Receptors in HIV Infection of Host Cells

Author

Robert W. Doms and Jacqueline D. Reeves

Subjects
biology, Chemokine receptor CCR5, viruses, virus diseases, Host tropism, CXCR4, Virology, Virus, Cell biology, Chemokine receptor, Viral replication, biology.protein, Tissue tropism, HIV tropism
Abstract

The discovery that HIV uses the chemokine receptors CCR5 and CXCR4 in conjunction with CD4 to infect cells helped explain viral tropism and pathogenesis. The expression pattern of CCR5 and CXCR4 coupled with their differential use by diverse virus strains largely explains HIV tropism, at least at the level of entry. Their discovery led directly to the identification of receptor-related polymorphisms that determine the genetic basis for the resistance to infection exhibited by some individuals and help explain the variable progression rates to AIDS of others. Subsequent structural studies have revealed the presence of highly conserved domains in the viral Env protein that are responsible for receptor binding and membrane fusion and that are real or potential targets for antiviral agents and neutralizing antibodies. The Env protein can also induce signaling via either CCR5 or CXCR4. While receptor signaling is not required for virus replication in transformed cell lines, it may modulate virus infection of primary cell types. The utilization of CCR5 and CXCR4 for the membrane fusion reaction is clear, but the role of signaling in the infection of primary cells is not and is clearly an area that requires further investigation.

Published
2003

2. Contributors

Author

John M. Abrams, John P. Adelman, Joseph L. Alcorn, Dario R. Alessi, Emil Alexov, Simon Alford, Kari Alitalo, James P. Allison, Steven C. Almo, Christelle Alory, Aymen Al-Shamkhani, Sally A. Amundson, Carl W. Anderson, Jannik N. Andersen, Peter Angel, Ettore Appella, William J. Arendshorst, Steve Arkinstall, Anjon Audhya, Joseph Avruch, Gary D. Bader, Cinzia Bagala, William E. Balch, Jesus Balsinde, Utpal Banerjee, David Barford, Dafna Bar-Sagi, Perry F. Bartlett, Philippe I.H. Bastiaens, Chiara Battelli, Linnea M. Baudhuin, Andrew J. Beavil, Rebecca L. Beavil, Joseph A. Beavo, Elsa Bello-Reuss, Stephen Bellum, Juan Carlos Izpisúa Belmonte, Craig B. Bennett, Jeffrey L. Benovic, Michael J. Berridge, Penny J. Beuning, Rashna Bhandari, Ananya Bhattacharya, Martin Biel, Vincent A. Bielinski, Hana Bilak, Lutz Birnbaumer, Geoff Birrell, Gail A. Bishop, Trillium Blackmer, Perry J. Blackshear, Christine Blattner, Mordecai P. Blaustein, Gary M. Bokoch, Lynda F. Bonewald, Marco Bonomi, Michelle A. Booden, Charles Boone, Martin D. Bootman, Johannes L. Bos, Jane M. Bradbury, Ralph A. Bradshaw, Anne R. Bresnick, Lena Brevnova, Ross I. Brinkworth, Michael S. Brown, Steven A. Brown, Anne Brunet, Robert Bucki, Robert D. Burgoyne, Janice E. Buss, Ronald A. Butow, Javier Capdevila, Ernesto Carafoli, Cathrine R. Carlson, Graham Carpenter, Juan J. Carrillo, Patrick J. Casey, William A. Catterall, Richard A. Cerione, Gianni Cesareni, Andrew C. Chan, Geoffrey Chang, Moses V. Chao, Harry Charbonneau, Philip Chen, Alan Cheng, Chris Chiu, Dar-chone Chow, Ted D. Chrisman, Anne Elisabeth Christensen, Jee Y. Chung, Grant C. Churchill, Aaron Ciechanover, Gino Cingolani, Sylvie Claeysen, Jean Closset, Shamshad Cockcroft, Patricia T.W. Cohen, Philip Cohen, Roger J. Colbran, Clay E.S. Comstock, Marco Conti, Jackie D. Corbin, Daniela Corda, Sabine Costagliola, Rick H. Cote, Shaun R. Coughlin, L. Ashley Cowart, Adrienne D. Cox, Mark S. Cragg, José L. Crespo, Claudia Crosio, Christopher Daly, Sami Damak, Mary Dasso, Michael David, Anthony J. Davis, Roger J. Davis, Richard N. Day, Eva Degerman, Warren L. DeLano, Mark L. Dell'Acqua, Emmanuèle Délot, Bruce Demple, Edward A. Dennis, John M. Denu, Anna A. DePaoli-Roach, Channing J. Der, Johan de Rooij, Frederic de Sauvage, Peter N. Devreotes, Valérie Dewaste, Robert B. Dickson, Becky A. Diebold, Pier Paolo Di Fiori, Maria Di Girolamo, Julie Diplexcito, Jack E. Dixon, Robert W. Doms, Daniel J. Donoghue, Russell F. Doolittle, Stein Ove Døskeland, Wolfgang R.G. Dostmann, Matthias K. Dreyer, Guo Guang Du, Keyong Du, Michael R. Duchen, William G. Dunphy, Joanne Durgan, Michael L. Dustin, Peter A. Edwards, Jackson G. Egen, Lee E. Eiden, Elaine A. Elion, Scott Emr, Othmar G. Engelhardt, Christophe Erneux, Peter J. Espenshade, Edward D. Esplin, B. Mark Evers, Joanne L. Eyles, Sheelagh Fame, Marilyn Farquhar, Robert Feil, Gui-Jie Feng, Stanley Fields, James J. Fiordalisi, Richard A. Firtel, Garret A. Fitzgerald, Andrew Flint, Marco Foiani, Barry Marc Forman, Albert J. Fornace, Sharron H. Francis, Günter Fritz, David A. Fruman, Antony Galione, Chris S. Gandhi, David L. Garbers, K. Christopher Garcia, Benjamin Geiger, Larry Gerace, Andrea Gerstner, Amato J. Giaccia, Michele Giannattasio, Vincent Giguère, Christopher K. Glass, Martin J. Glennie, Jennifer L. Glick, Joseph L. Goldstein, Venkatesh Gopal, Myriam Gorospe, Cedric Govaerts, Paul R. Graves, Patrick W. Gray, Irene Graziani, Douglas R. Green, Michael E. Greenberg, Iva Greenwald, Haihua Gu, Nuri Gueven, J. Silvio Gutkind, Jesper Z. Haeggström, Alan Hall, Michael N. Hall, Otto Haller, Heidi E. Hamm, Yusef A. Hannun, Carl A. Hansen, T. Kendall Harden, D. Grahame Hardie, Kiminori Hasegawa, Phillip T. Hawkins, Timothy A.J. Haystead, Xiao-lin He, Claus W. Heizmann, Carl-Henrik Heldin, Michelle L. Hermiston, Peter Herrlich, Elizabeth A. Hewat, Bertil Hille, Douglas J. Hilton, K.A. Hinchliffe, Steffan N. Ho, Su-Chin Ho, Mark Hochstrasser, Franz Hofmann, Christopher W. Hogue, Wim G.J. Hol, Jocelyn Holash, Robert A. Holmgren, Barry Honig, Bruce S. Hostager, Stevan R. Hubbard, Michael Huber, Tony Hunter, Anna Huttenlocher, Sarah G. Hymowitz, James N. Ihle, Jean-Luc Imler, R.F. Irvine, Ehud Y. Isacoff, Xavier Iturrioz, Lars F. Iversen, Ravi Iyengar, Stephen P. Jackson, Lily Yeh Jan, Fabiola Janiak-Spens, Paul A. Janmey, Peter Gildsig Jansen, Sophie Jarriault, Jonathan A. Javitch, Elwood V. Jensen, Kristen Jepsen, E. Yvonne Jones, Katherine A. Jones, J. Dedrick Jordan, Jomon Joseph, Louis B. Justement, Yariv Kafri, Richard A. Kahn, Shin W. Kang, Arthur Karlin, Heidi R. Kast-Woelbern, Randal J. Kaufman, Andrius Kazlauskas, James H. Keen, Rolf Kemler, Bruce E. Kemp, Mary B. Kennedy, Matthew A. Kennedy, Ushio Kikkawa, Albert H. Kim, Soo-A Kim, Sung-Hou Kim, Youngjoo Kim, Kirst King-Jones, Chris Kintner, Saul Kivimäe, Claude B. Klee, Rüdiger Klein, Thomas Kleppisch, Steven A. Kliewer, Richard A. Klinghoffer, Juergen A. Knoblich, Bostjan Kobe, George Kochs, Monica Kong-Beltran, Rolf König, Albert C. Koong, Murray Korc, Daniel Kornitzer, Anthony A. Kossiakoff, Jun Kotera, M.V. Kovalenko, Tohru Kozasa, Sergei Kozlov, Keith G. Kozminski, Sonja Krugmann, John Kuriyan, Riki Kurokawa, Peter D. Kwong, Wi S. Lai, Elise Lamar, Millard H. Lambert, David G. Lambright, Doron Lancet, Reiko Landry, Wallace Y. Langdon, Lorene K. Langeberg, Paul Lasko, Vaughn Latham, Martin F. Lavin, Kevin A. Lease, Hakon Leffler, Mark A. Lemmon, Ann E. Leonard, Alexander Levitzki, Hong-Jun Liao, Lucy Liaw, Giordano Liberi, Heiko Lickert, Robert C. Liddington, Thomas M. Lincoln, Jürgen U. Linder, Maurine E. Linder, Hui Liu, Zhengchang Liu, Marja K. Lohela, Sarah H. Louie, Deirdre K. Luttrell, Louis M. Luttrell, Karen M. Lyons, S. Lance Macaulay, Michael Maceyka, Thomas Maciag, Fernando Macian, Carol MacKintosh, David H. MacLennan, Nadir A. Mahmood, Craig C. Malbon, Sohail Malik, Orna Man, Carol L. Manahan, Anna Mandinova, Vincent C. Manganiello, James L. Manley, Matthias Mann, Gerald Manning, Ed Manser, Marta Margeta-Mitrovic, Robert F. Margolskee, Julia Marinissen, Roy A. Mariuzza, Mina D. Marmor, G. Steven Martin, Karen H. Martin, Sergio E. Martinez, Michael B. Mathews, Bruce J. Mayer, Mark L. Mayer, Maria R. Mazzoni, Frank McCormick, Clare H. McGowan, Melissa M. McKay, Wallace L. McKeehan, Alison J. McLean, Anthony R. Means, Ruedi Meili, Jingwei Meng, Mark Merchant, Frank Mercurio, Graeme Milligan, Guo-Li Ming, Daniel L. Minor, Nadeem Moghal, Neils Peter H. Møller, Marco Mongillo, Marc Montminy, Randall T. Moon, Richard I. Morimoto, Stephen E. Moss, Helen R. Mott, Carla Mouta, Marco Muda, Marc C. Mumby, Gretchen A. Murphy, Marco Muzi-Falconi, Raghavendra Nagaraj, Stefan R. Nahorski, Angus C. Nairn, Piers Nash, Benjamin G. Neel, Alexandra C. Newton, Yasutomi Nishizuka, Joseph P. Noel, Ellen A.A. Nollen, Irene M.A. Nooren, Rodney O'Connor, Stefan Offermanns, Tsviya Olender, Shao-En Ong, Darerca Owen, Lisa J. Pagliari, Lily Pao, John Papaconstantinou, Leonardo Pardo, Hay-Oak Park, Young Chul Park, Peter J. Parker, J. Thomas Parsons, J.M. Passner, Tony Pawson, Achille Pelliccioli, J. Regino Perez-Polo, Norbert Perrimon, Fabrice G. Petite, Emmanuel Petroulakis, Samuel L. Pfaff, Jacob Piehler, Linda J. Pike, Michael J. Pinkoski, Fiona J. Pixley, Paolo Plevani, Mu-ming Poo, Tullioi Pozzan, Stephen M. Prescott, Igor Prudovsky, James W. Putney, Thomas Radimerski, Elzbieta Radzio-Andzelm, Prahlad T. Ram, Lucia Rameh, Danica Ramljak, Barbara Ranscht, Anjana Rao, Carol J. Raport, Jacqueline D. Reeves, Holger Rehman, Trevor W. Reichman, Eric Reiter, Michael A. Resnick, Michael Reth, Sue Goo Rhee, Joel D. Richter, Rodney L. Rietze, James M. Rini, Jürgen A. Ripperger, Josep Rizo, Janet D. Robishaw, H. Llewelyn Roderick, Robert G. Roeder, Larry R. Rohrschneider, David Ron, Michael G. Rosenfeld, Hans Rosenfeldt, Kent L. Rossman, Christopher B. Roth, Markus G. Rudolph, Anja Ruppelt, Lino Saez, Thomas P. Sakmar, Guy S. Salvesen, Paolo Sassone-Corsi, Charles L. Saxe, Beat W. Schäfer, Ueli Schibler, Christian W. Schindler, Tobias Schmelzle, Sandra L. Schmid, Anja Schmidt, Eric F. Schmidt, Gideon Schreiber, Joachim E. Schultz, Beat Schwaller, Klaus Schwamborn, Thue Schwartz, William F. Schwindinger, Giorgio Scita, John D. Scott, Shaun Scott, Thomas Seebeck, Charles N. Serhan, John B. Shabb, Andrey S. Shaw, Stephen B. Shears, Shirish Shenolikar, Lei Shi, Chanseok Shin, Kazuhiro Shiozaki, Kevan M. Shokat, Trevor J. Shuttleworth, David P. Siderovski, Steven A. Siegelbaum, Adam M. Silverstein, Robert H. Singer, Michael K. Skinner, Jill K. Slack-Davis, Stephen J. Smerdon, Graeme C.M. Smith, Guillaume Smits, Sarah M. Smolik, Jessica E. Smotrys, Emer M. Smyth, Jason T. Snyder, Naoko Sogame, Raffaella Soldi, John Sondek, Nahum Sonenberg, Erica Dutil Sonneberg, Lindsay G. Sparrow, Sarah Spiegel, Stephen R. Sprang, Deepak Srivastava, Robyn L. Stanfield, E. Richard Stanley, Deborah J. Stauber, Christopher Stefan, Lena Stenson-Holst, Len Stephens, Paul W. Sternberg, Paul C. Sternweis, Ruth Steward, John T. Stickney, Andrew W. Stoker, Stephen M. Strittmatter, Beth E. Stronach, Roland K. Strong, Robert M. Stroud, Thomas C. Südhof, Roger K. Sunahara, Brian J. Sutton, Sipeki Szabolcs, Xiao-Bo Tang, Kjetil Taskén, Hisashi Tatebe, Servane Tauszig-Delamasure, Colin W. Taylor, Garry L. Taylor, Laura J. Taylor, Susan S. Taylor, George Thomas, Robert P. Thomas, E. Brad Thompson, Michael J. Thompson, Janet M. Thornton, Carl S. Thummel, Hideaki Togashi, Amy Hin Yan Tong, Nicholas K. Tonks, Peter Tontonoz, M.K. Topham, Knut Martin Torgersen, Hien Tran, Michel L. Tremblay, Ming-Jer Tsai, Sophia Y. Tsai, Susan Tsunoda, Stewart Turley, Darren Tyson, Robert L. Van Etten, Gilbert Vassart, Peter J. Verveer, Virginie Vlaeminck, Abraham M. de Vos, Ty C. Voss, Robert Walczak, Graham C. Walker, John C. Walker, Gernot Walter, Mark R. Walter, Fen Wang, Jean Y.J. Wang, Weiru Wang, Richard J. Ward, Philip Wedegaertner, Christian Wehrle, Arthur Weiss, Jamie L. Weiss, Alan Wells, Claudia Werner, Ann H. West, Marie C. Weston, John K. Westwick, Anders Wetterholm, Morris F. White, Malcolm Whitman, Matt R. Whorton, Christian Wiesmann, Roger L. Williams, William D. Willis, Timothy M. Willson, Ian A. Wilson, Ofer Wiser, Matthew J. Wishart, Alfred Wittinghofer, James R. Woodgett, David K. Worthylake, Jeffrey L. Wrana, Hao Wu, Yijin Xiao, H. Eric Xu, Yan Xu, Zheng Xu, Michael B. Yaffe, Kenneth M. Yamada, Seun-Ah Yang, Wannian Yang, Yosef Yarden, Hong Ye, Weilan Ye, Todd O. Yeates, Helen L. Yin, John D. York, Edgar C. Young, Kenneth W. Young, Matthew A. Young, Michael W. Young, Minmin Yu, Nathan R. Zaccai, Manuela Zaccolo, Eli Zamir, Mark von Zastrow, Chao Zhang, Xuewu Zhang, Zhong-Yin Zhang, Wenhong Zhou, and Roya Zoraghi

Published
2003

3. Functional characterization of novel G protein-coupled receptors involved in nociception and HIV-1 infection

Author

Marc Parmentier, Corinne Liesnard, Catherine Mollereau, Ronald G. Collman, Benjamin J. Doranz, Robert W. Doms, Françoise Liners, Yanjie Yi, Gilbert Vassart, Robert J. Smyth, Michel Samson, Joseph Rucker, Jean-Claude Meunier, Frédérick Libert, and Jean Costentin

Subjects
G protein-coupled receptor kinase, G protein, Heterotrimeric G protein, Class C GPCR, Immune receptor, Pharmacology, Biology, Receptor, Rhodopsin-like receptors, G protein-coupled receptor, Cell biology
Abstract

Publisher Summary This chapter discusses functional characterization of novel G protein-coupled receptors involved in nociception and HIV-1 infection. G protein-coupled receptors constitute the largest family of membrane receptors. G protein-coupled receptors share a common structural organization with seven transmembrane segments, and a common way of modulating cell function by regulating a limited number of effector systems through a family of heterotrimeric G-proteins. Due to these reasons, G protein-coupled receptors constitute major targets for therapeutic agents. Endogenous opioid peptides are widely distributed in the central and peripheral nervous systems and play important roles in modulating endocrine, cardiovascular, gastrointestinal, and immune functions. All three opioid receptors, δ, κ, and μ, are coupled to adenylyl cyclase and inhibit the formation of cAMP. The CHO-K1 cell line expressing the human recombinant ORL1 orphan receptor is used as a bioassay to detect a biological activity in extracts from rat brain. The biological activity is further purified to homogeneity by fast protein liquid chromatography (FPLC) and high-performance liquid chromatography (HPLC) fractionation.

Published
1997

5. Chapter 14 Expression of Foreign Proteins in a Human Neuronal System

Author

Virginia M.-Y. Lee, David G. Cook, and Robert W. Doms

Subjects
Neurite, Cell culture, Precursor cell, Protein targeting, medicine, Axoplasmic transport, Biology, medicine.disease_cause, Cell system, Cell biology
Abstract

Publisher Summary This chapter describes a recently developed model human neuronal system that makes it possible to obtain unlimited quantities of fully polarized, postmitotic neurons, and approaches that can be taken to express exogenous proteins transiently and to obtain stable cell lines. Thus, this system offers a way to study dendritic and axonal transport, membrane recycling, and protein targeting at the genetic and biochemical levels. The NT2N cell system offers an attractive way to overcome some of the technical limitations inherent in working with primary neuronal cultures. It is possible to obtain large quantities of neurons with which to perform biochemical experiments, and the growth of neurites can be synchronized and controlled by varying the substrate on which the cells grow. Because the differentiated NT2N neurons are derived from a mitotically active precursor cell line in vitro , it is possible to employ a variety of techniques that are not otherwise available when working directly with postmitotic neurons, to obtain expression of foreign proteins. Because they are fully polarized, NT2N cells offer a way to study protein sorting to axons and dendrites at both the biochemical and the morphological level.

Published
1994

6. [5] Protein conformational changes in virus-cell fusion

Author

Robert W. Doms

Subjects
chemistry.chemical_classification, Conformational change, Fusion, Cell fusion, Chemistry, Viral protein, Lipid bilayer fusion, Cleavage (embryo), medicine.disease_cause, Epitope, Biochemistry, medicine, Biophysics, sense organs, skin and connective tissue diseases, Glycoprotein
Abstract

Publisher Summary This chapter discusses the protein conformational changes in virus- cell fusion. With the techniques described in this chapter, it is possible to examine what happens to a relatively small region of the viral protein during its conformational change—that is, the loss of an antigenic epitope, or the exposure of a particular cleavage site or disulfide bond. Detailed kinetic studies, and perhaps the use of low temperatures, may reveal the sequence with which these rearrangements occur. In addition to describing aspects of the conformational change, it is necessary to ask whether the changes observed in an in vitro system are relevant for fusion in vitro. The conditions under which a given aspect of the conformational change occurs should reflect those under which fusion takes place. Most studies on the “acid” conformations of viral fusion proteins have examined structural changes that occur after acid treatment and reneutralization. The resulting structures may of course differ in important respects from the nascent molecules shortly after acid treatment.

Published
1993

7. [48] Oligomerization and protein transport

Author

Robert W. Doms

Subjects
Secretory protein, Membrane protein, Biochemistry, Chemistry, Endoplasmic reticulum, Biological membrane, Protein quaternary structure, Protein folding, Membrane transport, Transport protein
Abstract

Publisher Summary This chapter discusses several of the most commonly used methods to determine a protein's quaternary structure and the application of these techniques to correlate folding and assembly with transport. While studies on membrane proteins will be emphasized, the techniques are of course applicable to secretory proteins as well. It can be exceedingly difficult to ascertain the oligomeric structure of a protein complex consisting of noncovalently associated subunits. It is not uncommon for oligomers to dissociate following detergent solubilization, making analysis difficult at best. The chapter concludes with discussion that the commonly used biochemical techniques are more than adequate for studying protein folding and assembly in vivo , provided an appropriate degree of caution is exercised in interpreting the results. Studies directed along these lines will undoubtedly help elucidate the means by which proteins fold and assemble as well as the mechanisms that exist to govern transport of molecules from the endoplasmic reticulum (ER).

Published
1990

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