JC Virus Can Infect Human Immune and Nervous System Progenitor Cells:Implications for Pathogenesis

Jean Hou, Pankaj Seth and Eugene O. Major

Recent advances in stem cell biology have called attention to the role these cells may play in the pathogenesis of systemic and nervous system diseases. Although not capable of indefinite self renewal and pluripotentiality as stem cells are, progenitor cells can give rise to cells of different li...

Latent and Productive Polyomavirus Infections of Renal Allografts: Morphological, Clinical, and Pathophysiological Aspects

Volker Nickeleit, Harsharan K. Singh and Michael J. Mihatsch

Polyomavirus allograft nephropathy, also termed BK virus nephropathy (BKN) after the main causative agent, the polyoma-BK-virus strain, is a major complication following kidney transplantation. BKN is the most common viral infection affecting the renal allograft with a reported prevalence of 1% u...

Leflunomide in Solid Organ Transplantation and Polyoma Virus Infection

Michelle A. Josephson, Basit Javaid, Pradeep V. Kadambi, Shane M. Meehan and James W. Williams

Leflunomide, trade name Arava¨ (Aventis Pharmaceuticals Incorporation, Bridgewater, New Jersey, U.S.A.), belongs to a family of drugs called the malonitrilamides. Some, like leflunomide, have substantial immune suppressive activity in experimental allograft models. In addition to experimental dat...

Molecular Genetics of the BK Virus

Christopher L. Cubitt

The BK Virus (BKV) genome is a double-stranded, circular DNA molecule with genetic organization similar to other polyomaviruses, and high homology to JC Virus (JCV) and SV40. The archetypal form of BKV noncoding regulatory region (NCRR) is the infectious form of BKV that replicates in the urothe...

Molecular Recognition and Replication Enzymes

Esteban Domingo, Christof K. Biebricher, Manfred Eigen and John J. Holland.

The special chemistry of life is centrally governed by special biomacromolecules. These are built up as linear polymers from monomeric subunits: The key biopolymers are nucleic acids (deoxyribonucleic acid or DNA and ribonucleic acid or RNA) and proteins. Quite in contrast to industr...

Multiplication Strategies of RNA Genetic Elements

Esteban Domingo, Christof K. Biebricher, Manfred Eigen and John J. Holland.

The main steps in the life cycle of a virus are (Figure. 2.1): receptor and coreceptor recognition at the cell surface, entry into the cell, uncoating and release of the genetic material, viral gene expression, viral genome replication, assembly of progeny particles, and exit from ...

Pharmacotherapeutic Options for the Management of Human Polyomaviruses

Julie Roskopf, Jennifer Trofe, Robert J. Stratta and Nasimul Ahsan

Polyomaviruses [BK virus (BKV), JC virus (JCV) and simian virus 40 (SV40)] have been known to be associated with diseases in humans for over thirty years. BKV-associated nephropathy and JCV-induced progressive multifocal leukoencephalopathy (PML) were for many years rare diseases occurring only i...

Phylogenomics and Molecular Evolution of Polyomaviruses

Keith A. Crandall, Marcos Perez-Losada, Ryan G. Christensen, David A. McClellan and Raphael P. Viscidi

We provide in this chapter an overview of the basic steps to reconstruct evolutionary relationships through standard phylogeny estimation approaches as well as network approaches for sequences more closely related. We discuss the importance of sequence alignment, selecting models of evolution, an...

Phylogeny of Human Endogenous and Exogenous Retroviruses

Aris Katzourakis and Michael Tristem

The human genome contains a number of human endogenous retrovirus (HERV) families, each resulting from a single germ-line infection. Here we combine information on all previously described HERV families, and further search the human genome sequencing project databases to add taxa to taxon poor ar...

Polyomavirus in Human Cancer Development

Winston Lee and Erik Langhoff

In animal studies, polyoma viruses have been found to be viral agents for oncogenesis and to produce a wide range of pathological lesions in experimental animals, including a variety of neoplastic tumors. The human polyoma viruses (JCV and BKV), along with their simian cousin (SV40), are ubiquito...

Polyomavirus-Associated Nephropathy in Renal Transplantation: Critical Issues of Screening and Management

Hans H. Hirsch*, Cinthia B. Drachenberg, Juerg Steiger and Emilo Ramos

Polyomavirus-associated nephropathy (PVAN) is an emerging disease in renal transplant patients with variable prevalence of 1-10% and graft loss up to 80%. BK virus (BKV) is the primary etiologic agent, but JC virus (JCV) and possibly simian virus SV40 may account for some cases. Intense immunosup...

Polyomaviruses and Human Diseases

Nasimul Ahsan and Keerti V. Shah

Polyomaviruses are small, nonenveloped DNA viruses, which are widespread in nature. In immunocompetent hosts, the viruses remain latent after primary infection. With few exceptions, illnesses associated with these viruses occur in times of immune compromise, especially in conditions that bring ab...

Population Dynamics and Virus Adaptability

E.Domingo, C.K. Biebricher, M. Eigen, J.J. Holland

The meaning of fitness of living organisms has evolved since the time of Darwin (Reznick and Travis, 1996). The concept has broadened from referring to the survival of an individual to meaning its lifetime reproductive success. The latter, in turn, encompasses a number of elements su...

Quantitative Molecular Evolution

E.Domingo, C.K. Biebricher, M. Eigen, J.J. Holland

Darwinian evolution, instrumental in the qualitative description of many phenomena in Biology, can and should also be formulated quantitatively. Darwin himself cited the population growth law described by Thomas R. Malthus in An Essay on the Principle of Population G...

Receptor-Mediated HIV Entry

Dimitrov, Dimiter S., Christopher C. Broder

Entry of enveloped viruses into cells can be conveniently divided into three main stages: first, attachment to the cell surface, second, fusion of the viral with the cellular membrane, and third, uncoating of the virus envelope and release of the nucleocapsid into the cytoplasm (Fig. 8.1). In thi...

Receptors and Virus Infections

Dimitrov, Dimiter S. , Christopher C. Broder

Many (but not all) viruses have evolved to utilize a variety of cell surface molecules for gaining access into the cellular interior. A striking feature of virus adaptation to hosts under selective pressures is the absence of any obvious relationship between receptor molecular structure or physio...

Retroviruses, Their Domesticated Relatives and Other Retroinvaders: Potential Genetic and Epigenetic Mediators of Phenotypic Variation

Eugene D. Sverdlov

This chapter is a very brief introduction to exogenous and endogenous retroviruses and other genomic mobile elements whose mobility is conditioned by transient passage through an RNA stage. This passage is mediated by transcription of the element with host cell RNA polymerase, followed by reverse...

Serological Cross Reactivity Between Polyomavirus Capsids

Raphael P. Viscidi and Barbara Clayman

Multiple methods have been used to measure antibodies to polyomavirus virions. In order to have a common method for all polyomaviruses, we developed enzyme im munoassays (EIAs) using virus-like-particles (VLPs) produced in the baculovirus expression system. We tested serum samples from humans and...

Serological Diagnosis of Human Polyomavirus Infection

Annika Lundstig and Joakim Dillner

Measurement of antibody titres to the human polyomaviruses BK and JC has for many years had to rely on Haemagglutination inhibition. In recent years, viral serology based on virus-like particles (VLPs) in enzyme immunoassays (EIAs) has become widely used for a variety of viruses. We sought to est...

Signal Transduction in Osteoclast Biology: The OPG-RANKL-RANK Pathway

Ji Li

Skeletal homeostasis is maintained by a delicate balance between bone-resorbing osteoclasts and bone-building osteoblasts. Recently, three novel tumor necrosis factor (TNF) ligand and receptor family members have been identified as critical extracellular regulators of bone resorption: osteop...

Soluble Chemokine Binding Proteins Encoded by Viruses

Vincent P. Smith, Neil A. Bryant and Antonio Alcami

Chemokines are chemoattractant cytokines that regulate trafficking and effector functions of leukocytes, and play a key role in inflammation and host defence against invading pathogens.1,2 For a detailed description of the chemokine family see chapter 1. The induction of particular chemokines ...

Structure and Replication of Hepatitis Delta Virus RNA

John M. Taylor

This review focuses on the RNAs of HDV, with emphasis on RNA structure, RNA transcription, and post-transcriptional RNA processing. Included is an evaluation of two current models of HDV RNA replication.

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T3/T7 DNA Packaging

Philip Serwer

During formation of a mature bacteriophage particle, a procapsid of protein packages the linear double-stranded DNA genome of the related bacteriophages, T3 and T7. Initiation of T3/T7 DNA packaging in vivo occurs near the genetic right end of a concatemer-associated genome. Initiation in vivo re...

The Chemokines: What Are They and What Do They Do?

Shaun R. McColl

Whole body coverage by leukocytes is a critical feature of immunity. Various leukocyte populations flow through the peripheral blood, and depending on whether they encounter appropriate signals, they may move into inflamed tissues to deal with infections as is the case with myeloid cells, or into va...

The Fusion Cofactors/Coreceptors

Dimitrov, Dimiter S. , Christopher C. Broder

The principal cell types targeted by HIV-1 in vivo are helper T lymphocytes and cells of the monocyte-macrophage lineage via the CD4 receptor pathway, the primary high affinity receptor for HIV-1.1-3 The HIV-1 envelope glycoprotein serves two functions that are critical in the replication cycle o...