Viruses are major pathogens in humans, and in the organisms with which we share this planet. The massive health and economic burden these agents impose has spurred a huge research effort to understand their most intimate details. One outcome of this effort has been the production, in many but certainly not all cases, of effective vaccines and therapies. - other consequence has been the realization that we can exploit viruses and put them to work on our behalf. Viruses are still seen to have the most - tential as vehicles for gene delivery and other therapeutic applications. However, their ability to exploit cellular functions to their own ends makes viruses not only highly effective pathogens but also exquisite experimental tools. Work with viruses underpins much of our current understanding of molecular cell biology and related fields. For membrane traffic in parti- lar, viruses have been crucial in providing insights into key cellular fu- tions and the molecular mechanisms underlying these events.

Successful viral infection, replication, and dissemination depend on the ability of a virus to subvert host cell processes. The molecular interplay between viruses and their hosts is an ancient and ongoing evolutionary "arms race," with each side constantly evolving new strategies to outwit the other. The existing literature regarding the impact of viral conflicts on mammalian evolution has predominantly concentrated on proteins that are directly involved in immune responses. Thus, in known cases of host-virus interactions, we see evolutionary signatures of conflict in host genes that encode viral antagonists. However, the principles of natural selection postulate that this paradigm is not exclusive to immune genes. Instead, we can infer that any protein interacting with viruses is subject to the selective pressures driving genetic adaptation. As such, we reasoned that genes involved in the active transport of macromolecules within the cell are one potential source of conflict. Due to the large size of eukaryotic cells, along with the high density of macromolecules, diffusion is limited. Cells transport intracellular cargo using dynein and kinesin motors, which move on microtubules in opposite directions to overcome this diffusion-limited environment. Viruses co-opt this cellular machinery for cellular entry, the transportation of viral components to replication sites, remodeling of cellular compartments, and viral egress. Conversely, the host adaptive and innate immune responses require movement of signaling components, transport of endocytic and exocytic vesicles, organelle recycling, and cellular remodeling, all of which require the microtubule-based trafficking machinery. Motivated by the competing interest of microtubule-based transport in aiding and inhibiting viral replication, we set out to identify conflicts over the intracellular trafficking machinery between viruses and their host cells. In this dissertation, I present collaborative work that identifies several intracellular trafficking genes exhibiting evolutionary signatures of conflict. Of these candidate genes, I characterize a novel role in the innate antiviral immune response for ninein-like (NINL), a dynein activating adaptor. Overall, this work provides a glimpse into the impact that viruses may have on the evolution of the intracellular transport machinery and demonstrates how leveraging evolutionary signatures of conflict can uncover novel host-pathogen interactions that could become therapeutic targets.

Molecular Regulation of Endocytosis is a compilation of scientific "short stories" about the entry of external substances into cells. As one can see from the chapters, endocytosis regulates diverse processes such as homeostasis of the cell, signal transduction, entry of pathogens and viruses. In addition to the experimental techniques embedded in each chapter, entire chapters are dedicated to experimental approaches that will be useful to all scientists and their model systems. For those more clinically oriented, the final chapters look to the future and ways of utilizing endocytic pathways for therapeutic purposes.

This comprehensive account of the human herpesviruses provides an encyclopedic overview of their basic virology and clinical manifestations. This group of viruses includes human simplex type 1 and 2, Epstein–Barr virus, Kaposi's Sarcoma-associated herpesvirus, cytomegalovirus, HHV6A, 6B and 7, and varicella-zoster virus. The viral diseases and cancers they cause are significant and often recurrent. Their prevalence in the developed world accounts for a major burden of disease, and as a result there is a great deal of research into the pathophysiology of infection and immunobiology. Another important area covered within this volume concerns antiviral therapy and the development of vaccines. All these aspects are covered in depth, both scientifically and in terms of clinical guidelines for patient care. The text is illustrated generously throughout and is fully referenced to the latest research and developments.

Microbes have co-evolved over time with other organisms to the extent that some are so acquainted with host cell biology that they subvert key cellular processes with unrivalled precision. This volume reviews this exciting new discipline, reflecting the recent explosion of knowledge as well as broader insights into fundamental cellular processes. C. David O'Connor and David Smith cover the salient aspects by using a range of model systems.

This book is centered on a comprehensive list of MHC peptide motifs and ligands as known to date, together with selected T cell epitopes, arranged in an easy-to-read fashion. This information is put into context by chapters on MHC gene organization, MHC structure, T cell epitope prediction, antigen processing and T cell responses. In addition, the book provides a great deal of complementary information: amino acid sequences of MHC class I alpha1 and alpha2 domains and of class II alpha1 and beta1 domains, the established or predicted composition and specificity of MHC pockets, notes on MHC nomenclature including old assignments and reference to useful internet addresses. A handy reference manual that should be helpful for all those dealing with MHC-associated peptides.