CRC - Cell Death During HIV Infection

Organization: CRC
Publication Date: 29 November 2005
Page Count: 561


Establishing that the human immunodeficiency virus (HIV) is the etiologic agent of acquired immunodeficiency syndrome (AIDS) was the beginning of a revolution in science. Since then, the advances made in retrovirology have led to major advances in therapy for HIV, which, in turn, have allowed thousands worldwide to live longer lives. The advances in immunologic sciences have been rapid as well, and within a few short years, those advances will likely translate into immune-based therapies for use in clinical practice. In comparison, the study of apoptosis dysregulation during HIV-induced immunodeficiency has been less intense. Nevertheless, important lessons have been learned. Most scientists and clinicians now accept that cell death is not a passive process but, rather, a tightly coordinated and regulated one. As such, apoptotic cell death may be amenable to therapeutic intervention. In non-HIV disease states, clinical trials of apoptosis modifying agents used for HIV disease are already underway.

In HIV disease, enhanced understanding of the apoptotic pathways that are involved may lead to novel treatment strategies. It is apparent, however, that multiple, likely simultaneous, processes contribute to the enhanced CD4 T cell apoptosis, which together contribute to immune deficiency. In all likelihood, apoptotic dysregulations are cell-type dependent, because those cells that become latent reservoirs for HIV, by definition, do not succumb to the proapoptotic effects of infection. Such complexities offer multiple avenues for intervention: antiapoptotic approaches to limit HIVinduced T cell depletion and proapoptotic approaches designed to eradicate latent infections.

When I was approached by Taylor & Francis regarding this project, I envisioned soliciting coauthors who were conducting the most current and exciting bench science in apoptosis and HIV. I have taken their work and attempted to form a volume that may be used both as a reference source and as an incubator to stimulate future work. Thus, the book is divided into four sections: Basic Concepts, Mechanisms of HIV-Associated Cell Death, Clinical Consequences of HIV-Induced Cell Death, and Therapeutic Issues. Section 2, Mechanisms of HIV-Associated Cell Death, has three component parts: Viral Factors, Immune Mechanisms, and Infected vs. Uninfected Death.

Each of the authors in this book is a leader in his or her respective field. Their efforts ensure that each chapter meets the highest standards of scientific scholarship. I gratefully recognize those efforts and am sure that they will be appreciated by readers as well. I am indebted to them all.

I am equally indebted to the contributions of my many collaborators, colleagues, and past, present, and future members of my laboratory who were, over the years, a source of personal and professional inspiration and motivation. Early in my medical career, I was involved in the care of an HIV-positive patient at a time when no effective therapies existed and none were in development. The sense of hopelessness then and, again, more recently in the era of antiretroviral resistance was a recurring source of motivation to increase my understanding of the disease. To these patients and the numerous other patients who volunteered for clinical- and laboratory-based studies, I offer my sincere thanks and best wishes.

I also wish to thank Mark McClees and Carrie Rogness, from Mayo Clinic's Division of Infectious Diseases, for their efforts in assembling this edition and working with the contributing authors and publisher. Without their efforts, this volume would not be in print.

Finally, I acknowledge the support and love of my parents, my wife Nanci, and my children, Lauren, Andrew, Adrianne, and Caitlin. Their patience and understanding have allowed me to pursue my passions and obsessions; to each, I am eternally indebted.