Guide to Clinical and Diagnostic Virology (eBook)

Reeti Khare (Autor)

eBook Download: EPUB

2019
John Wiley & Sons (Verlag)
9781683672920 (ISBN)

Infos

The explosion in clinical testing has been especially rapid in virology, where emerging viruses and growing numbers of viral infections are driving advances. The Guide to Clinical and Diagnostic Virology offers a digestible view of the breadth and depth of information related to clinical virology, providing a practical, working knowledge of the wide array of viruses that cause human disease.

Introductory chapters cover the basics of clinical virology and laboratory diagnosis of infections, including virus structure, life cycle, transmission, taxonomy, specimen types and handling, and a comparison of assays used for detection. Detailed sections on important topics include

• Viral pathogens and their clinical presentations
• Diagnostic assays and techniques, including culture-based, immunological, and molecular
• Prevention and management of viral infections, with guidance on biosafety, vaccines, and antiviral therapies
• The regulatory environment for laboratory testing, including regulatory requirements and assay performance and interpretation

Critical concepts are carefully curated and concisely summarized and presented with detailed illustrations that aid comprehension, along with important highlights and helpful hints. These features, plus question sections that reinforce significant ideas and key concepts, make this an invaluable text for anyone looking for an accessible route through clinical and diagnostic virology. Laboratory technologists, medical students, infectious disease and microbiology fellows, pathology residents, researchers, and everyone involved with viruses in the clinical setting will find the Guide to Clinical and Diagnostic Virology an excellent text as well as companion to clinical virology references.

Autor

Reeti Khare, PhD, D(ABMM), is the Director of Microbiology at Northwell Health Laboratories in New York. She received her PhD in Virology and Gene Therapy at Mayo Clinic and did a postdoctoral fellowship at the University of Washington. Her research involved reengineering viral vectors, developing adenoviruses for liver gene therapy, and creating viral vector vaccines against MRSA. She returned to Mayo Clinic for her clinical microbiology fellowship and is a diplomate of the American Board of Medical Microbiology. Reeti enjoys teaching and learning about microbiology and has authored numerous publications, chapters, and reviews. At Northwell Health Labs she continues to pursue clinical research and provide student education, and is responsible for laboratory oversight, improving efficiency, designing workflows, and diagnostic microbiology testing.

Textauszug

 

CHAPTER 1

INTRODUCTION TO VIRUSES

I. OVERVIEW. Viruses are obligate intracellular parasites. Unlike all other organisms, they are not “alive” because they are metabolically inactive on their own. They are also not “dead” because they can metabolize and reproduce when associated with a host cell. Instead, they are referred to as being “active” or “inactive.” Viruses are difficult to study because of their minuscule size, but they are even more abundant than bacteria. Most are part of normal environmental or human flora but some viruses are medically relevant and can cause infections that fall anywhere on the spectrum, from asymptomatic to fulminant. Several factors affect the pathogenicity of a virus.

1. Virus-specific factors

• Virulence: Some viruses are more virulent than others. For example, rabies virus is highly pathogenic, while torque teno virus does not cause disease despite being ubiquitous in normal flora.
• Persistence: Some viruses, like herpesviruses, cause mild disease but infect humans for life.
• Indirect effects: Viruses like bacteriophages only infect bacteria but are still indirectly pathogenic to humans. For example, Corynebacterium diphtheriae does not generally cause clinically significant disease unless it is infected with the bacteriophage containing the diphtheria toxin gene.

2. Host-specific factors: Hereditary genetic mutations can allow viruses that are weakly pathogenic to cause significant disease. For example, a specific mutation in CCR5 (a host cell receptor for HIV) has been shown to prevent infection with this virus. On the other hand, other mutations can result in overgrowth of viruses. For example, human papillomavirus 2 (HPV2) typically causes benign warts, but individuals with genetic defects in cell-mediated immunity can demonstrate uncontrolled giant warty overgrowths (“tree man” disease).

3. Immunosuppression: Immunosuppressive drugs, virus-induced immunosuppression, and even pregnancy are all instances in which the immune system is depressed. This can leave patients vulnerable to unique viral infections.

II. VIRUS STRUCTURE. The structure of a virus defines its life cycle, mechanism of pathogenicity, and how it is detected by laboratory assays. A virus particle, or virion, is composed of nucleic acid surrounded by a protective protein coat called a capsid. Together, the nucleic acid and capsid are called the nucleocapsid.

1. Capsids: Occur in three main shapes (Fig. 1.1).

Figure 1.1. Viral capsids come in three main shapes.

• Polyhedral capsids have multiple flat sides that form a rigid shell around the viral nucleic acid. Viruses with lots of flat sides can appear round. Viruses with these kinds of capsids are highly regular and have a rigid shape and size. Most DNA viruses are polyhedral.
• Helical capsids wrap proteins around the strand of nucleic acid to form a spiral, elongated nucleocapsid. These viruses tend to be more variable in size and shape. Most RNA viruses are helical.
• Complex capsids have other shapes or are a combination of helical and polyhedral capsids.

2. Envelopes: Some viruses have an envelope, which is a lipid bilayer that surrounds the nucleocapsid.

Most blood-borne viruses are enveloped because they need to evade the immune system efficiently.

• Envelopes are acquired from cell membranes and act as a shield from the immune system. The disadvantage is that these viruses are susceptible to detergents, drying, and pH changes and typically do not survive for long on external surfaces.
• Nonenveloped, or naked, viruses are more resistant to harsh conditions and tend to be more stable in the environment. They are relatively resistant to disinfectants (e.g., alcohol, dilute bleach, quaternary ammonium compounds, and even water disinfectants like chlorine). This means that they are difficult to eliminate from community and hospital environments.

Most gastrointestinal viruses are naked because they must be highly resistant to the acidic environment of the stomach.

3. Size: Viruses cannot be seen using light microscopes. Medically important viruses range from ∼20 to 500 nm in length (Fig. 1.2).

Figure 1.2. Comparison of sizes. Viruses are ~10 times smaller than a bacterium and ~100 times smaller than a eukaryotic cell.

Rule of thumb: Viruses are about 1/10 the size of a bacterial cell.

III. LIFE CYCLE. The life cycle of the virus is how it binds to a host cell, replicates its nucleic acid, and then spreads to new cells. Knowing each virus’s life cycle is critical to understanding what part of the body will be affected, how long the infection will last, how it can be detected, and which antivirals will work.

Replication: making new genomes.

Transcription: making messenger RNA (mRNA) from the genome.

Translation: making proteins from mRNA.

1. Incubation period: Viruses infect target host cells and replicate. Due to the low level of virus at the beginning of infection, patients are typically asymptomatic.

2. Spread: Viruses spread through the host by infecting adjacent cells, traveling in migratory cells, disseminating through the bloodstream (viremia), and diffusing through body fluids. Viremia can be identified through detection of viral nucleic acids and/or antigens in the blood.

• Viruses infect cells by binding to specific cellular receptors; cells that do not display the correct receptors will not be infected. Tropism is the affinity of a virus for some cell types and not others.
• Once bound, virions enter cells by endocytosis or fusion. During endocytosis, the host cell membrane invaginates and engulfs the virus. During fusion, the viral envelope will fuse with the cell membrane in order to release the viral nucleocapsid into the cell.

3. Prodromal phase: Viruses may produce early, nonspecific symptoms (e.g., fever, aches, pain, and nausea) as they replicate.

• Once inside the cell, viruses replicate, transcribe mRNA, and translate it into viral proteins. These proteins and nucleic acids are assembled into infectious viral particles in the nucleus or cytoplasm.
• These viral aggregates can sometimes be seen as viral inclusions.

4. Active disease: Viruses cause an immediate or long-lived infection in the cell.

• Lytic viruses lyse (destroy) the host cell to get out immediately after replication. This manifests as an acute infection where the patient may show characteristic signs of the viral infection.
• Lysogenic viruses cause a long-lived, latent infection by integrating into the host genome. These infections are often subclinical. Environmental triggers can cause the integrated viruses to excise and enter the lytic cycle. The integrated viral genome is called a provirus. Proviral DNA replicates passively with the cell every time the host cell replicates. This makes them very long-lived and largely undetected by the immune system.

Proviruses = integrated viral genomes

• Pseudolysogenic or episomal viruses persist for a long time in the host cell without integrating. Their nucleic acids remain separate as an episome. These episomes are diluted as cells divide and removed from circulation when cells die (Fig. 1.3).

Episomes = nonintegrated, persistent viral genomes

Figure 1.3. Integration versus episomal persistence. Episomes are diluted when the cell replicates while integrated viruses are multiplied when the cell replicates.

Latent viruses are dormant. They do not actively produce virions or trigger the immune system, and therefore result in a persistent viral reservoir.

• Depending on the type of virus, new viral particles will exit the cell by four main methods (Fig. 1.4).

Figure 1.4. Methods of viral release from a cell. (A) Lysis; (B) budding; (C) exocytosis; (D) cell-to-cell transport within syncytia.

• Lysis: bursting of the host cell
• Budding: Viruses push into the perimeter of the cell and capture part of the cellular membrane. Many enveloped viruses surround their nucleocapsid with the host plasma membrane in order to evade detection by the immune system.
• Exocytosis: Virions are enclosed in a cellular vesicle, which then fuses with the plasma membrane in order to release virus particles outside the cell.
• Cell-to-cell transport: Some viruses can cause host cells to fuse together (syncytia). This allows the new viruses to directly enter neighboring cells without exposing them to the immune system.

5. Resolution of disease: Both the innate and adaptive immune responses clear or suppress the viral infection.

• Innate responses are able to suppress viral infections rapidly.

• Antiviral cytokines, like interferon, are produced. They activate lymphocytes and upregulate proteins that...

Produkt-Details

• Erscheint lt. Verlag: 1.3.2019
• Reihe/Serie: ASM
• Reihe/Serie: ASM
• Reihe/Serie: ASM Books
• Sprache: englisch
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete
• Themenwelt: Naturwissenschaften ► Biologie ► Genetik / Molekularbiologie
• Schlagworte: baltimore classification • Biowissenschaften • classification • Clinical • Clinical Virology • Diagnosis • Diagnostik • infectionsdifferential • Klinische Virologie • Laboratory • Life Sciences • Medical Science • Medizin • Microbiology • Microbiology & Virology • Mikrobiologie • Mikrobiologie u. Virologie • Nomenclature • Viral • Virologie • Virology • virusesvirus structure
• ISBN-13: 9781683672920 / 9781683672920