This compendium presents some of the major applications of neutron scattering techniques to problems in biology. It is a record of the papers presented at the Neutrons in Biology Conference, the third in an occasional series held to highlight progress in the field and to provide a focus for future direction. The strength ofthe neutron scattering technique remains principally in the manipula tion of scattering density through hydrogen and deuterium atoms. The development ofad vanced detectors, innovative instrument and beamline components, and sophisticated data acquisition systems through the 1970s and early 1980s provided a sound foundation for the technique. With continued development, some of the exotic and expensive equipment has become affordable by the medium-sized facilities, thereby broadening the user base considerably. Despite problems with the major neutron sources in the late 1980s and early 1990s, some spectacular results have been achieved. Whilst the high and medium flux beam reac tors will continue to make a major impact in the field, the results from the first experi ments, and the planned developments on spallation neutron sources, clearly indicate that the technique has enormous potential.

The articles in this volume provide a comprehensive overview of our current understanding of the roles played by cellular factors in the early steps of retroviral replication. A better understanding of these functions will provide critical new insights into retrovirus-host cell interactions and is likely to prove useful for the future development of effective antiretroviral therapies.

The time seems ripe for a critical compendium of that segment of the biological universe we call viruses. Virology, as a science, having passed only recently through its descriptive phase of naming and num hering, has probably reached that stage at which relatively few new-truly new-viruses will be discovered. Triggered by the in tellectual probes and techniques of molecular biology, genetics, biochemical cytology, and high-resolution microscopy and spectroscopy, the field has experienced a genuine information explo sion. Few serious attempts have been made to chronicle these events. This comprehensive series, which will comprise some 6000 pages in a total of about 22 volumes, represents a commitment by a large group of active investigators to analyze, digest, and expostulate on the great mass of data relating to viruses, much of which is now amorphous and disjointed, and scattered throughout a wide literature. In this way, we hope to place the entire field in perspective, and to develop an in valuable reference a*nd sourcebook for researchers and students at all levels. This series is designed as a continuum that can be entered anywhere, but which also provides a logical progression of developing facts and integrated concepts.

Salmonella infections of man and animals continue to be a distressing health problem worldwide. Far from disappearing, the incidence of typhoid fever in developing countries may be far higher than we had imagined. Salmonella food poisoning has increased to one of the major causes of gastroenteritis in the developed world, in itself also an indication that animal salmonellosis is still a major cause for concern. The situation requires a concerted multidisciplinary research effort in order to generate the new information and technology needed to assist in the control of these diseases. This concept was the driving force behind the NATO Advanced Research Workshop on "Biology of Salmonella" held at Portorosa, Messina, Italy, May 11-15, 1992. With additional support from the University of Messina, Medeva Group Research (UK) and the Swiss Serum and Vaccine Research Institute, the meeting brought together epidemiologists, microbiologists, molecular biologists, immunologists and clinicians. All the participants were actively working on different but related aspects of Salmonella and salmonellosis, with most of the leading laboratories worldwide being represented. The workshop provided an excellent opportunity for interdisciplinary consultation; it is not often that the topic of Salmonella and salmonellosis is covered to such breadth and depth in one extended meeting. Keynote addresses by invited speakers were interspersed with offered papers, many by younger members of the scientific community, and this volume presents the collated manuscripts of the lectures and extended summaries of the offered papers.

The field of bacterial genetics has been restricted for many years to Escherichia coli and a few other genera of aerobic or facultatively anaerobic bacteria such as Pseudomonas, Bacillus, and Salmonella. The prevailing view up to recent times has been that anaerobic bacteria are interesting organisms but nothing is known about their genetics. To most microbiologists, anaerobic bacteria appeared as a sort of distant domain, reserved for occasional intrusions by taxonomists and medical microbiologists. By the mid-1970s, knowledge of the genetics and molecular biology of anaerobes began to emerge, and then developed rapidly. but also im This was the result of advances in molecular biology techniques, portantly because of improvements in basic techniques for culturing anaerobes and for understanding their biochemistry and other areas of in terest. Investigations in this field were also stimulated by a renewal of interest in their ecology, their role in pathology and in biotransformations, and in the search for alternative renewable sources of energy. The initial idea for this book came from Thomas D. Brock. When Dr. Brock requested my opinion about two years ago on the feasibility of publishing a book on the genetics of anaerobic bacteria, as a part of the Brock/Springer Series in Contemporary Bioscience, I answered positively but I was apprehen sive about assuming the role of editor. However, I was soon reassured by the enthusiastic commitment of those I approached to contribute. Eventually, thanks to the caring cooperation of the contributors, the task became relatively easy.

An extensive assessment of combination therapy of AIDS. Main focus is put on the Highly Active Antiretroviral Therapy (HAART) but other therapies like salvage therapy are also discussed. The chapters cover efficacy, treatment, causes of treatment failure, clinical care, guidelines, pharmacology. The volume closes with an outlook on future perspectives.

Marek's disease virus (MDV) is a herpesvirus which causes a lymphoproliferative disorder of the domestic chicken worldwide. This serious economical problem caused by MDV was mostly solved by development of an effective vaccine against MDV. The development of live vaccines against the disease is remarkable as it has led to the first example of a commercially available vaccine against cancer as well as against diseases caused by herpesviruses.
This volume gives an overview on many aspects of MDV research and summarizes recent advances in the field. The topics include the history, biology, and molecular biology of MDV, pathogenesis, vaccinal immunity, immune response, genetic resistance and development of recombinant polyvalent vaccines. It is hoped that this volume will make an important contribution towards the control of infectious diseases.

Viruses are studied either because they cause significant human, animal or plant disease or because they are useful materials for probing basic phenomena in biology, chemistry, genetics and/or molecular biology. Arenaviruses are unusually interesting in that they occupy both categories. Arenaviruses cause several human diseases known primarily as the hemorrhagic fevers occurring in South and Latin America (Bolivia: Machupo, Argentine, Junin virus, and Brazil: Sabia virus) and in Africa (Lassa fever virus). Because such viruses produce profound disabilities and often kill the persons they infect, they are a source of health concern and economic hardship in the countries where they are prevalent. Further, they provide new problems for healthcare persons owing to the narrowing of the world as visitors from many countries travel increasingly to and from endemic areas and may incubate the infectious agent taking it from an endemic area into an area where the virus is not expected. Such cases are now being re corded with increasing frequency. In addition to these hemor rhagic fever viruses, the arenavirus lymphocytic choriomeningitis virus (LCMV) can infect humans worldwide, although the illness is most often less disabling and severe than those elicited by the other arenaviruses. Yet, LCMV is of greater concern to non arenavirologists and experimentalists using tissue culture or ani mals, etc. , because normal-appearing cultured cells or tissues from animals used for research may be persistently infected with LCMV without manifesting clinical disease or cytopathology and may transmit that infection to laboratory workers.

Forty years after the discovery of the helix nature of DNA and more than twenty after the first applications of recombinant DNA technology to the pharmaceutical industry, the Pandora's vase of biotechnology seems far from being empty. New products for agriculture and the food industry are constantly being placed on the market, and powerful monitoring techniques have been developed to track non-modified and genetically modified vaccines, viruses, microbes and plants released into the environment. Molecular approaches for taxonomic purposes, which might also be useful for quality control and assurance, have been successfully developed and used for taxonomic purposes in the last decade for both prokaryotic and eukaryotic cells, including yeasts and filamentous fungi. Mycorrhizae are one example of a traditional biotechnology that can greatly benefit from the latest molecular approaches. These universal symbioses between soil fungi and plant roots playa central role in most of the natural and agricultural ecosystems in such key processes as nutrient cycling, soil structural conservation and plant health. For these reasons, mycorrhizae have been successfully used to improve the quality of forest and agricultural seedlings, to produce high-quality micropropagated plants and to increase the production of edible mushrooms of high economic value, such as truffles. However, although controlled inoculation of oak and hazel seedlings with ectomycorrhizal truffles has been carried out for decades in France and Italy, and is still expanding commercially, several technological gaps remain to be filled.

Infection Control in the ICU Environment provides the details of the most common infection control problems facing intensive care units. Authors include noted scientists, intensivists and epidemiologists from the United States and Europe as well as infection control experts from the Centers for Disease Control and Prevention. Acinetobacter, methicillin resistant staphylococcus aureus and vancomycin resistant enterococci are examined in detail. This volume also includes cutting edge information regarding the potential for prophylactic and pre-emptive therapy of fungal infections in intensive care units. Innovations in vascular catheter care and prevention of bloodstream infections are discussed in this volume as well as the newest information in mathematical modeling to understand the epidemiology and control of infections in intensive care units.

In the past half century, filamentous fungi have grown in commercial importance not only in the food industry but also as sources of pharmaceutical agents for the treatment of infectious and metabolic diseases and of specialty proteins and enzymes used to process foods, fortify detergents, and perform biotransformations. The commercial impact of molds is also measured on a negative scale since some of these organisms are significant as pathogens of crop plants, agents of food spoilage, and sources of toxic and carcinogenic compounds. Recent advances in the molecular genetics of filamentous fungi are finding increased application in the pharmaceutical, agricultural, and enzyme industries, and this trend promises to continue as the genomics of fungi is explored and new techniques to speed genetic manipulation become available. This volume focuses on the filamentous fungi and highlights the advances of the past decade, both in methodology and in the understanding of genomic organization and regulation of gene and pathway expression.

There is considerable interest in thermophile microorganisms, in their environments, their ability to survive at temperatures which normally denature proteins, but more importantly, as a valuable resource for bio technology. The first reported isolation of Thermus by Tom Brock was in 1969. This initiated the present era of thermophilic research with the realization that where liquid water is available, there may be no limits to the temper ature at which microorganisms can grow. Considerable research into the ecology, physiology, metabolism, and thermostable enzymes of thermo philes has led to their evaluation for a range of industrial and commercial processes. The past fifteen years have been an explosive period of dis covery of many new genera and species, including the descriptions of a new fundamental kingdom-the Archaea. Much of the current research has been focused on the Archaea; but it is significant that during this period, the original type strain YT-l of Thermus aquaticus described by Brock has provided a major step forward in molecular biology. DNA polymerase from strain YT-I has proved to be the major success in the commercialization of enzymes from thermophilic microorganisms to date. The ease with which Thermus strains can be handled in laboratories without specialized equipment, together with the large investment in de scribing their structure, metabolism, and genetics, should ensure a con tinuing effort in Thermus research.

Much research over the past 30 to 40 years has shown that the inflammatory response, while critical for host defense during microbial infection, may itself play a central role in the pathogenesis of sepsis. Although key mediators responsible for this injury have been identified, efforts clinically to augment our conventional antimicrobial and supportive therapies during sepsis with agents modulating the inflammatory response have been unsuccessful. As a result, the mortality associated with this lethal syndrome, especially when complicated by shock, has remained persistently high. Unfortunately, during this same period of time, the incidence of sepsis has accelerated as other fields of medicine have relied increasingly on therapies that predispose to infection. While frustrating, overall this experience in the field of sepsis has not been without value. Most importantly, it has helped define on several different levels the complexity of the septic patient. Recognizing and addressing this complexity as discussed by each of the contributors to Evolving Concepts in Sepsis and Septic Shock may now provide new inroads into the treatment of sepsis.

In 1996 the International Committee for Taxonomy of Viruses (ICTV) recognized the name Nidovirales, as the formal name for Coronaviridae and A rteriviridae. In recognition of this change, and in response to the wishes of our colleagues we named this meeting for the first time "The International Symposium of Nidoviruses". The meeting in the wooded environment of Lake Harmony, Pennsylvania, provided a stimulating opportunity for assessing the progress made in the field since the last meeting in Segovia Spain in 1997. Over 150 scientists from academia and industry attended the meeting. The meeting hosted senior members of the Nidovirus community, some of whom have been studying the subject for over 20 years, as well as younger scientists, the next generation of Nidoviro10gists. The traditional informal format, the shared meals, the social activities and the relatively inexpensive venue made the meeting a popular adventure. In her opening remarks Susan Weiss showed pictures from previous meetings, reminding us how young we used to look. Neal Nathanson was our keynote speaker at the opening night, giving an overview on how viral pathogenesis studies helped in shaping the evolution of viral research and vaccine development. The scientific program of the meeting was divided into 9 sessions including lO keynote presentations. The meeting opened with a session on epidemiology, evolution and genome structure. Sasha Gorbalenya shared with us insights gained from comparative sequence analysis, emphasizing the unifying traits among nidovriuses, but also pointed out the remaining "black holes".

As discussed in this book, a large body of evidence indicates that selenium is a cancer chemopreventive agent. Further evidence points to a role of this element in reducing viral expression, in preventing heart disease, and other cardiovascular and muscle disorders, and in delaying the progression of AIDS in HIV infected patients. Selenium may also have a role in mammalian development, in male fertility, in immune function and in slowing the aging process. The mechanism by which selenium exerts its beneficial effects on health may be through selenium-containing proteins. Selenium is incorporated into protein as the amino acid selenocysteine. Selenocysteine utilizes a specific tRNA, a specific elongation factor, a specific set of signals, and the codeword, UGA, for its cotranslational insertion into protein. It is indeed the 21st naturally occurring amino acid to be incorporated into protein and marks the first and only expansion of the genetic code since the code was deciphered in the mid 1960s.

Assembling the latest research by an international group of contributors, this volume covers the epidemiology, pathogenesis, clinical features, and control measures of this elusive microorganism. It will provide a deeper understanding of the pathogen to physicians and surgeons caring for patients infected, or at risk of becoming infected, with Pseudomonas Aeruginosa.

The Annexins is focused on a specific family of calcium and membrane-binding proteins, annexins, ubiquitously spread within living organisms, including animals, plants and fungi. The volume covers important areas of annexinology. The characterization of structural-functional relationship within the annexin family of proteins, together with emerging transgenic animal models, provides an up-to-date overview of potential physiological roles of annexins. Growing evidence of participation of annexins in human diseases, called annexinopathies, related to disturbances in signal transduction, vesicular traffic, ion homeostasis and energy metabolism within the cell. The book will attract a broad scientific audience, not only scientists interested in annexins, but also others involved in multidisciplinary studies, as well as undergraduate and postgraduate students. It can be used in courses relating to special topics such as calcium homeostasis, calcium-binding proteins, membrane structure and transport properties, various signal transduction pathways, and membrane trafficking.

Heat shock proteins (HSP) have received ample interest by immunologists over recent years. Initially they were found to be dominantly immunogenic microbial antigens. The connection with inflammation was established when it was uncovered that T cells specific for these antigens have a crucial role in the induction and regulation of experimental arthritis. Since then, the raised presence of immunity to HSPs in virtually all conditions of inflammation, including autoimmune diseases, transplant rejection and atherosclerosis, has emphasised the critical significance of immunity to HSPs in inflammatory diseases.

In this volume, a distinguished international group of contributors present the latest molecular, organismal, and epidemiological research on arenaviruses. Their work will broaden both the clinician's and the researcher's knowledge of basic mechanisms of immunological tolerance, viral immunosuppression, the nature of protective immune responses to vaccination, and viral effects on cell functions.

The genus Aspergillus has a worldwide distribution and is one of the most common of all groups of fungi. They are possibly the greatest contami nants of natural and man-made organic products, and a few species can cause infections in man and animals. The aspergilli are also one of the most important mycotoxin-producing groups of fungi when growing as contaminants of cereals, oil seeds, and other foods. Not all aspergilli are viewed as troublesome contaminants, however, as several species have had their metabolic capabilities harnessed for commercial use. The aspergilli have long been associated in the Far East with the koji stage of several food fermentations, particularly soy sauce and miso, and subsequently as a source of useful enzymes. The ability of these fungi to produce several organic acids, especially citric acid, has created major industrial complexes worldwide. Traditional methods of strain develop ment have been extensively studied with the industrial strains, while more recently, recombinant DNA technology has been applied to the aspergilli with emphasis on heterologous protein production. In compiling this book, I have been fortunate to have the full enthu siastic involvement of the authors, and to them I extend my very grateful thanks for mostly being on time and for producing such readable and authoritative chapters. Collectively, we hope that our efforts will strengthen the scientific understanding of this intriguing group of filamentous fungi and further their use in the field of biotechnology.

The NATO Advanced Research Workshop entitled "The Photosynthetic Bacterial Reaction Center: Structure, Spectroscopy, and Dynamics" was held May 10-15, 1992, in the Maison d'H6tes of the Centre d'Etudes Nuc1eaires de Cadarache near Aix-en-Provence in the south of France. This workshop is the most recent of a string of meetings which started in Feldafing (Germany) in March 1985, soon after the three-dimensional structure of the bacterial reaction center had been elucidated by X-ray crystallography. This was followed, in September 1987, by a workshop in Cadarache and, in March 1990, by a second meeting in Feldafing. Although one of the most important processes on Earth, photosynthesis is still poorly understood. Stimulated by the breakthrough of solving the bacterial reaction center structure at atomic resolution, the field of relating this structure to the function of the reaction center, i. e. the remarkably efficient conversion and storage of solar energy, has been developing vigorously. Once the general organization of the cofactors and some details of the protein-cofactor interactions were known, it became possible to combine a variety of spectroscopic techniques with the powerful tool of site-directed mutagenesis in order to address increasingly incisive questions about the specific role of some amino acid residues in the electron transfer process. Still another promising tool is being developed, namely the exchange of a number of the native bacteriochlorophyll and bacteriopheophytin cofactors by chemically modified pigments.

Varicella-zostervirus(VZV)isamedicallyimportanthumanherpesvirus,belo- ingtothesubfamilyAlphaherpesviridae. Thecapacitytopersistinsensoryneurons isade?ningcharacteristicoftheAlphaherpesviridaesubgroupwhichalsoincludes herpessimplexvirus1and2;likeVZV,simianvaricellavirus(SVV),pseudorabies virus-1(PRV-1),andequineherpesvirus-1(EHV-1)belongtotheVaricellovirus genus. ThebasicelementsoftheinfectiouscycleofVZVinthehumanhostarethat infectionofthena?vehostresultsinvaricella,commonlyknownaschickenpox, latencyisestablishedinsensoryganglia,andreactivationcauseszosteror"sh- gles. "Therelationshipbetweenthecausative agentofvaricellaandzoster was demonstratedmorethan100yearsagowhenchildreninoculatedwithmaterialfrom zosterlesionswereshowntodevelopvaricella. Thelocalizeddistributionofthe zosterrashwasalsorecognizedasdemarcatingthedematomeinnervatedbyaxons fromneuronsineachofthesensoryganglia. Earlyelectronmicroscopystudies showedthatvirusparticleswerepresentinhighconcentrationsinthevesicular ?uidfrombothvaricellaandzosterlesions,andVZVwasamongthe?rstviruses propagatedinvitrobyJohnEndersandThomasWeller. Theintroductionofim- nosuppressivetherapiesformalignancyledtoobservationssuggestingtheneed forcell-mediatedimmunityinthehostresponsetovaricellaanditsroleinma- tainingVZVlatency. Fortunately,earlystudiesofthemolecularvirologyofVZV revealedthatitwasinhibitedbyinterferencewiththethymidinekinasegene,and thelife-threateningandoftenfatalVZVinfectionsexperiencedbythesepatients becametreatablewithantiviraldrugs. Subsequently,thecapacitytogrowVZVin tissueculturewasexploitedtocreatealiveattenuatedVZVvaccinebyMichiaki Tashihaki. Whilenowtakenforgranted,theseearlyinsightsaboutVZVandits characteristicsasahumanpathogenaswellasthedevelopmentofeffectivean- viral drugs and vaccines occurred over many decades. Importantly, these early observationssetthestagefortheremarkableprogressthathasbeenmadeinour understandingofthemolecularbiologyofVZV,thesubtletiesofitstropismfor differentiatedhumancells,includinglymphocytesaswellasskinandneurons,and themechanismsbywhichthevirusachievesanequilibriumwiththehostsothatit persistsnotjustintheindividualbutinthehumanpopulation. v vi Preface Thepurposeofthisvolumeistoreviewkeyareasofprogressinthe?eldofVZV research,aswellasworkontherelatedSVV,writtenbythosewhohavecontributed manyofthenew? ndingsthathaveenrichedourknowledgeoftheuniquech- acteristicsofthisubiquitoushumanpathogen. AlthoughtheVZVgenomeisthe smallestamongthehumanherpesviruses,therapidlyacceleratingpaceofdiscovery about VZV and VZV-host interactions re?ected in these reviews promises to continueasnewtoolsareavailableandnewhypothesesaregeneratedtoexplain howVZVhascreatedandmaintaineditsnicheinthehuman"virome"Therelationshipbetweenthecausative agentofvaricellaandzoster was demonstratedmorethan100yearsagowhenchildreninoculatedwithmaterialfrom zosterlesionswereshowntodevelopvaricella. Thelocalizeddistributionofthe zosterrashwasalsorecognizedasdemarcatingthedematomeinnervatedbyaxons fromneuronsineachofthesensoryganglia. Earlyelectronmicroscopystudies showedthatvirusparticleswerepresentinhighconcentrationsinthevesicular ?uidfrombothvaricellaandzosterlesions,andVZVwasamongthe?rstviruses propagatedinvitrobyJohnEndersandThomasWeller. Theintroductionofim- nosuppressivetherapiesformalignancyledtoobservationssuggestingtheneed forcell-mediatedimmunityinthehostresponsetovaricellaanditsroleinma- tainingVZVlatency. Fortunately,earlystudiesofthemolecularvirologyofVZV revealedthatitwasinhibitedbyinterferencewiththethymidinekinasegene,and thelife-threateningandoftenfatalVZVinfectionsexperiencedbythesepatients becametreatablewithantiviraldrugs. Subsequently,thecapacitytogrowVZVin tissueculturewasexploitedtocreatealiveattenuatedVZVvaccinebyMichiaki Tashihaki. Whilenowtakenforgranted,theseearlyinsightsaboutVZVandits characteristicsasahumanpathogenaswellasthedevelopmentofeffectivean- viral drugs and vaccines occurred over many decades. Importantly, these early observationssetthestagefortheremarkableprogressthathasbeenmadeinour understandingofthemolecularbiologyofVZV,thesubtletiesofitstropismfor differentiatedhumancells,includinglymphocytesaswellasskinandneurons,and themechanismsbywhichthevirusachievesanequilibriumwiththehostsothatit persistsnotjustintheindividualbutinthehumanpopulation. v vi Preface Thepurposeofthisvolumeistoreviewkeyareasofprogressinthe?eldofVZV research,aswellasworkontherelatedSVV,writtenbythosewhohavecontributed manyofthenew?ndingsthathaveenrichedourknowledgeoftheuniquech- acteristicsofthisubiquitoushumanpathogen. AlthoughtheVZVgenomeisthe smallestamongthehumanherpesviruses,therapidlyacceleratingpaceofdiscovery about VZV and VZV-host interactions re?ected in these reviews promises to continueasnewtoolsareavailableandnewhypothesesaregeneratedtoexplain howVZVhascreatedandmaintaineditsnicheinthehuman"virome"sos- cessfully. Further improvements in the clinical management of VZV infection shouldemergeinparallelwithbetterinsightsintoVZVmolecularvirologyand pathogenesis. Stanford,CA,June,2010 AllisonAbendroth AnnM. Arvin JenniferF. Moffat Contents TheVaricella-ZosterVirusGenome ...1 JeffreyI. Cohen VZVMolecularEpidemiology ...15 JudithBreuer RolesofCellularTranscriptionFactorsinVZVReplication ...43 WilliamT. Ruyechan EffectsofVaricella-ZosterVirusonCellCycleRegulatoryPathways ...67 JenniferF. MoffatandRebeccaJ. Greenblatt Varicella-ZosterVirusOpenReadingFrame66ProteinKinase andItsRelationshiptoAlphaherpesvirusUS3Kinases ...79 AngelaErazoandPaulR. Kinchington VZVORF47SerineProteinKinaseandItsViralSubstrates ...99 TeriK. KenyonandCharlesGrose OverviewofVaricella-ZosterVirusGlycoproteinsgC,gHandgL ...113 CharlesGrose,JohnE. Carpenter,WallenJackson,andKarenM. Duus AnalysisoftheFunctionsofGlycoproteinsEandIandTheirPromoters DuringVZVReplicationInVitroandinSkinandT-CellXenografts intheSCIDMouseModelofVZVPathogenesis ...129 AnnM. Arvin,StefanOliver,MikeReichelt,JenniferF. Moffat, MarvinSommer,LeighZerboni,andBarbaraBerarducci Varicella-ZosterVirusGlycoproteinM ...147 YasukoMoriandTomohikoSadaoka vii viii Contents VaricellaZosterVirusImmuneEvasionStrategies ...155 AllisonAbendroth,PaulR. Kinchington,andBarrySlobedman VZVInfectionofKeratinocytes:ProductionofCell-FreeInfectious VirionsInVivo ...173 MichaelD. GershonandAnneA. Gershon Varicella-ZosterVirusTCellTropismandthePathogenesis ofSkinInfection ...189 AnnM. Arvin,JenniferF. Moffat,MarvinSommer,StefanOliver, XibingChe,SusanVleck,LeighZerboni,andChia-ChiKu ExperimentalModelstoStudyVaricella-ZosterVirusInfection ofNeurons ...211 MeganSteain,BarrySlobedman,andAllisonAbendroth MolecularCharacterizationofVaricellaZosterVirusinLatently InfectedHumanGanglia:PhysicalStateandAbundanceofVZV DNA,QuantitationofViralTranscriptsandDetection ofVZV-Speci?cProteins ...229 YevgeniyAzarkh,DonGilden,andRandallJ. Cohrs NeurologicalDiseaseProducedbyVaricellaZosterVirusReactivation WithoutRash ...2 43 DonGilden,RandallJ. Cohrs,RaviMahalingam,andMariaA. Nagel Varicella-ZosterVirusNeurotropisminSCIDMouse-Human DorsalRootGangliaXenografts ...255 L. Zerboni,M. Reichelt,andA. Arvin RodentModelsofVaricella-ZosterVirusNeurotropism ...277 JeffreyI. Cohen SimianVaricellaVirus:MolecularVirology ...291 WayneL. Gray SimianVaricellaVirusPathogenesis ...309 RaviMahalingam,IlhemMessaoudi,andDonGilden Varicella-ZosterVirusVaccine:MolecularGenetics ...323 D. ScottSchmid VZVTCell-MediatedImmunity ...341 AdrianaWeinbergandMyronJ. Levin Contents ix PerspectivesonVaccinesAgainstVaricella-ZosterVirusInfections ...359 AnneA. GershonandMichaelD. Gershon Index ...373 . Contributors Allison Abendroth Department of Infectious Diseases and Immunology, UniversityofSydney,BlackburnBuilding,Room601,Camperdown,NSW 2006, Australia and Centre for Virus Research, Westmead Millennium Institute,Westmead,NSW2145,Australia,allison. abendroth@sydney. edu. au AnnM. Arvin StanfordUniversitySchoolofMedicine,G311,Stanford,CA 94305,USA,aarvin@stanford.

These Proceedings of the Fourth International Congress on the Cornea continue a tradition of summarizing the state-of-the art basic and clinical research in cornea and ex- ternal diseases since the first Congress was held in 1964. Reflecting the emerging impor- tance of refractive surgery, two of the twelve sessions of the Congress were devoted to refractive surgery; this is reflected in an emphasis in these Proceedings. In addition, an en- tire session was devoted to the molecular and cellular biology of the cornea with impor- tant new information on the role of growth factors and cytokine modulation of corneal wound healing. Within these Proceedings an international group of expert researchers and practitioners provide the latest insights into the tear film and ocular surface, corneal trans- plantation and eyebanking, the corneal stroma and endothelium, contact lenses, microbial and nonmicrobial keratitis, keratoconus, and world corneal health. Notable subjects covered include the latest understanding of the barrier function of the ocular surface epithelium, corneal hydration control, the molecular mechanisms con- trolling gene expression in corneal wound healing, stromal~pithelial interactions in the cornea, the immunology of blepharitis, the effect of contact lenses on the conjunctiva, morphologic and functional evaluation of the human corneal endothelium, long-term fol- low-up of penetrating keratoplasty in keratoconus, the Tampa trephine penetrating kerato- plasty, and the refractive results of the Nidek EC-5000 excimer laser.

Fluorescence is a very powerful tool for work at the frontier of cell biology, photobiology and bioinstrumentation. The stated aim of the workshop was to highlight the significance of fluorescence work for the understanding of cell and tissue physiology, physiopathology and pharmacology, particulary in terms of the analytical use of fluorescent probes in oncology. In the organization of the workshop a multidisciplinary approach was selected. The purpose of the Advanced Research Workshop (ARW) was to bring together researchers in the various disciplines of tissue optics, imaging, microspectrofluorometry and state of the art probes, in order to explore the full benefits that can be derived in biomedicine through the convergence of these approaches. When applied to in vivo and in situ studies, fluorescence and related optical methods enable us to explore within tissues, cells and organelles photon effects previously understood only in solution photochemistry. Processes which can be studied at the molecular level by photophysics, photochemistry and physical chemistry can be evaluated in living tissue by fluorescence spectroscopy and imaging at the intracellular level in terms of structure and function. Thus, fluorescence adds a new dimension to cell biology and physiology. This approach is now supported by a full and versatile, rapidly growing armamentarium of new selective probes for organelles, enzymes, cations, cytoskeleton and metabolic control.