Review
Abstract
Research into the pathogenesis, prevention, and control of infectious and parasitic diseases remains a global priority, as these scourges continue to be a substantial cause of mortality and morbidity. The plethora of molecular tools that are now readily available has facilitated a genome-wide approach to studying the pathogenesis of such diseases, with direct implications for disease prevention and treatment. The articles in this Review Series describe how genome-wide approaches have provided insight into a range of human pathogens, leading to greater understanding of the human diseases that they cause, and highlight some of the challenges that must be overcome if we are to maximize what we learn from the wealth of genomic information now available.
Authors
Karen Honey
Abstract
Staphylococcus aureus is the leading cause of bacterial infections in developed countries and produces a wide spectrum of diseases, ranging from minor skin infections to fatal necrotizing pneumonia. Although S. aureus infections were historically treatable with common antibiotics, emergence of drug-resistant organisms is now a major concern. Methicillin-resistant S. aureus (MRSA) was endemic in hospitals by the late 1960s, but it appeared rapidly and unexpectedly in communities in the 1990s and is now prevalent worldwide. This Review focuses on progress made toward understanding the success of community-associated MRSA as a human pathogen, with an emphasis on genome-wide approaches and virulence determinants.
Authors
Frank R. DeLeo, Henry F. Chambers
Abstract
The increasing availability of complete genome sequences of RNA viruses has the potential to shed new light on fundamental aspects of their biology. Here, I use case studies of 3 RNA viruses to explore the impact of genomic sequence data, with particular emphasis on influenza A virus. Notably, the studies of RNA virus genomics undertaken to date largely focused on issues of evolution and epidemiology, and they have given these disciplines new impetus. However, genomic data have so far made fewer inroads into areas of more direct importance for disease, prevention, and control; thus, harnessing their full potential remains an important goal.
Authors
Edward C. Holmes
Abstract
Vaccination has played a significant role in controlling and eliminating life-threatening infectious diseases throughout the world, and yet currently licensed vaccines represent only the tip of the iceberg in terms of controlling human pathogens. However, as we discuss in this Review, the arrival of the genome era has revolutionized vaccine development and catalyzed a shift from conventional culture-based approaches to genome-based vaccinology. The availability of complete bacterial genomes has led to the development and application of high-throughput analyses that enable rapid targeted identification of novel vaccine antigens. Furthermore, structural vaccinology is emerging as a powerful tool for the rational design or modification of vaccine antigens to improve their immunogenicity and safety.
Authors
C. Daniela Rinaudo, John L. Telford, Rino Rappuoli, Kate L. Seib
Abstract
Molecular pathogenomic analysis of the human bacterial pathogen group A Streptococcus has been conducted for a decade. Much has been learned as a consequence of the confluence of low-cost DNA sequencing, microarray technology, high-throughput proteomics, and enhanced bioinformatics. These technical advances, coupled with the availability of unique bacterial strain collections, have facilitated a systems biology investigative strategy designed to enhance and accelerate our understanding of disease processes. Here, we provide examples of the progress made by exploiting an integrated genome-wide research platform to gain new insight into molecular pathogenesis. The studies have provided many new avenues for basic and translational research.
Authors
James M. Musser, Samuel A. Shelburne III
Hepatitis C virus versus innate and adaptive immune responses: a tale of coevolution and coexistence
Abstract
Since the identification of the hepatitis C virus (HCV) 20 years ago, much progress has been made in our understanding of its life cycle and interaction with the host immune system. Much has been learned from HCV itself, which, via decades of coevolution, gained an intricate knowledge of host innate and adaptive immune responses and developed sophisticated ways to preempt, subvert, and antagonize them. This review discusses the clinical, virological, and immunological features of acute and chronic hepatitis C and the role of the immune response in spontaneous and treatment-induced HCV clearance.
Authors
Barbara Rehermann
Abstract
Muscle fiber deterioration resulting in progressive skeletal muscle weakness, heart failure, and respiratory distress occurs in more than 20 inherited myopathies. As discussed in this Review, one of the newly identified myopathies is desminopathy, a disease caused by dysfunctional mutations in desmin, a type III intermediate filament protein, or αB-crystallin, a chaperone for desmin. The range of clinical manifestations in patients with desminopathy is wide and may overlap with those observed in individuals with other myopathies. Awareness of this disease needs to be heightened, diagnostic criteria reliably outlined, and molecular testing readily available; this would ensure prevention of sudden death from cardiac arrhythmias and other complications.
Authors
Lev G. Goldfarb, Marinos C. Dalakas
Abstract
Intermediate filaments (IFs) are abundant structures found in most eukaryotic cells, including those in the nervous system. In the CNS, the primary components of neuronal IFs are α-internexin and the neurofilament triplet proteins. In the peripheral nervous system, a fifth neuronal IF protein known as peripherin is also present. IFs in astrocytes are primarily composed of glial fibrillary acidic protein (GFAP), although vimentin is also expressed in immature astrocytes and some mature astrocytes. In this Review, we focus on the IFs of glial cells (primarily GFAP) and neurons as well as their relationship to different neurodegenerative diseases.
Authors
Ronald K.H. Liem, Albee Messing
Abstract
Epidermolysis bullosa (EB) simplex is a rare genetic condition typified by superficial bullous lesions that result from frictional trauma to the skin. Most cases are due to dominantly acting mutations in either keratin 14 (K14) or K5, the type I and II intermediate filament (IF) proteins tasked with forming a pancytoplasmic network of 10-nm filaments in basal keratinocytes of the epidermis and in other stratified epithelia. Defects in K5/K14 filament network architecture cause basal keratinocytes to become fragile and account for their trauma-induced rupture. Here we review how laboratory investigations centered on keratin biology have deepened our understanding of the etiology and pathophysiology of EB simplex and revealed novel avenues for its therapy.
Authors
Pierre A. Coulombe, Michelle L. Kerns, Elaine Fuchs
Abstract
Intermediate filaments (IFs) are encoded by the largest gene family among the three major cytoskeletal protein groups. Unique IF compliments are expressed in selective cell types, and this expression is reflected in their involvement, upon mutation, as a cause of or predisposition to more than 80 human tissue-specific diseases. This Review Series covers diseases and functional and structural aspects pertaining to IFs and highlights the molecular and functional consequences of IF-associated diseases (IF-pathies). Exciting challenges and opportunities face the IF field, including developing both a better understanding of the pathogenesis of IF-pathies and targeted therapeutic approaches.
Authors
M. Bishr Omary
No posts were found with this tag.
Copyright © 2024 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)