TEXTBOOK

OF

VIROLOGY

DR. VINOD SINGH · Associate Professor·. · Department of MicrobiologyBarkatullah University, Bhopal (M.I'.) India

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Science and technology are constantly changing fields. New research and experience broaden the scope of information and knowledge. The authors have tried their best in giving information available to them while preparing the material for this book. Although, all efforts have been made to ensure optimum accuracy of the material, yet it is quite possible some errors might have been left uncorrected. The publisher, the printer and the authors will not be held responsible for any inadvertent errors, omissions or inaccuracies.

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Preface

Since long I was feeling the need of text book of virology for the postgraduate as well as undergraduate students of paramedical, medical and basic microbiology of various teaching organizations. A lacuna has always been .sensed particularly in the areas of diagnostics and therapeuttcvirology.·Keepingthe students demand of biomedical sciences, microbiology, biotechnology, nursing, physiotherapy, dental and other allied courses I took the decision to extend my limited knowledge to students. I have tried my best to include basic mechanisms of Life cycle, pathogenesis, diagnosis, immunity and structural aspects of viruses of diversified families, detailed caricature and illustration have also been framed to simplify the subject in depth ..

I am indebted to many stalwarts in my profession for their valuable guidance, their books and publications in relevant journals which I have consulted freely, if . some reference has been omitted due to oversight I would request the readers to .please bring this to the attention of e publisher who will ensure that full acknowledgement is made in subsequent editions. The help provided by my students specially Desh Deepak Singh, Sarika Am:dekar and other research scholars, colleagues and librarian for preparing this book is acknowledged, without which this difficult task could not have been completed. Suggestion and additional information will always be welcomed from . readers for further improvement. Lastly I would like to extend my special thanks tomy family members whose constant support and motivation made this book possible.

Vinod Singh

AJ>out the Author

Dr. Vinod Singh is currently Associate Professor with Department of Microbiology of Barkatullah University, Bhopal, M.P,India. His areas of specialization are Microbiology and Immunology. He has a long experience of working in areas of Clinical and Diagnostic Microbiology. He did his Post Graduate in Life Sciences with specialization in Immunology and Clinical Biochemistry from Institute of Life Sciences of CSJM University, Kanpur and Doctorate in Serology and Immunology from Department of Medicine of King George Medical College (KGMC),Lucknow.

He started his Research carrier working in the area of Immunology on the project sponsored by Department of Atomic Energy (DOE) of India on Study of Effect of Chronic and Acute Microwave Radiation on Immunological System of Belgian White Rabbits at Electrical Engineering Department of Indian Institute of Medical Sciences (I.LT) Kanpur, and after that on the Role of Antinuclear Antibodies (ANA) specifities in the Patients of Systemic Lupus Erythromatosous(SLE) and Rheumatoid Arthritis from Clinical Immunology Unit of Department of All India Institute of Medical Sciences ( A.1.1.M.S) New Delhi.

Dr Singh also worked as Senior Project Associate in the International Development Research Council (1.D.R.C) Canada funded project of Development of Low Cost Water filter against Rota Virus at Environmental Engineering Department of Indian Institute of Technology (1.1.T),Kanpur and on the Clinical, Immunological and Virological study in Patients of Dialated Cardio Myopathic Patients caused by Coxsackie virus from Virology Department of All India Institute of Medical Sciences, New Delhi.

He did his postdoctoral work on Walter Reed Army Research Institute,USA funded project on Effect of a Interferon on murine Malaria and clone drug resistant species of Lesihmania donovani from the division of Microbiology and Parasitology of Central Drug Research Institute (C.D.R.I), Lucknow.

Dr Singh also served as a Senior Assistant Professor at Department of Microbiology of Cancer Hospital and Research Institute, Gwalior and was associated with Laboratory Services of Microbiology and Immunology. There his main focus was on the diagnosis of Pathogenic Bacterial species from Clinical isolates and monitoring of Tumor from various categories of Cancer patients. He was also member of Tumor Board of Cancer Hospital.

He was also involved in teaching the 'Pbst Graduate programme of Medical Microbiology and Immunology. He was a1so Recipient of Best Teacher Award by Gwalior Development Commeettee.

Dr Singh was also an Executive member of Indian Immunology Society (I.LS), Member of International Union of Immunology Society (LU.I.S) and presently joint secretary of Society for Immunology and Immunopathology (SJ.LP). He is also a reviewer of Journal of Rheumatology published by British Society of Rheumatology, U.K, International Dairy Research Journal, Denmark and Journal of Antimicrobial Agent, USA. Internatimial Journal of Immunopathology and pharmacology.

He as been the Associate Editor of Journal of Immunology and Immunopathology pubUsehd . by. Society . · of Immunology ·and Immunpathology(SIIP),and Journal of BioSciences ,ITRC, India. He has published several research papers in field of Microbiology and Immunology in reputed journals.

Chapter 1 Chapter 2 Chapter 3Chapter 4 Chapter 5 Chapter 6Chapter 7 Chapter 8Chapter 9Chapter 10Chapter 11 Chapter 12 Chapter 13

. Chapter 14 Chapter 15 Chapter 16 Chapter 17 Chapter 18 Chapter 19 Chapter 20 Chapter 21 Chapter 22 Chapter23 Chapter 24 Chapter 25

. Chapter 26 Chapter 27 Chapter 28

Chapter29_ _ Chapter 30

Chapter31 Chapter 32 Chapter 33 Index

Contents

Introduction to Virology Structure and Oassification of Viruses Multiplication Viral Genetics Effects on Cells Epidemiology and Evolution Control of Viral Infections and Diseases Chemotherapy of Viral Infections Immune Defenses Nonspecific Defenses Viral Pathogenesis Adenoviruses Hepatitis Viruses Herpesviruses Orthomyxoviruses

1 5

19 35 45 59 71

81 ,·91 109 123 135 149 173 193

Paramyxoviruses 205 Picomaviruses 229 Rhabdoviruses: Rabies Virus 245 Poxviruses 257

· Rotaviruse, Reoviruses, Coltiviruses, and Orbiviruses 265 Parvoviruses 283 Filoviruses 291 Togaviruses: Rubella Virus 307 Arenaviruses 319 Bunyaviruses 329

--Corona viruses . _ . 341 _· Norwalk Virus and Other Caliciviruses · 347 Tumor Viruses 353 Papovaviruses 387 Alphaviruses (Togaviridae) and Flaviviruses (Flaviviridae) 405 Human Retroviruses 427 . Subacute Spongiform Unconventional Virus Encephalopathies 449

Persistent Viral Infections 467

483

Chapter 1

Introduction to Virology

Epidemiologic studies show that viral infections in developed countries are the most common cause of acute disease that does not require hospitalization In developing countries, viral diseases also exact a heavy toll in mortality and permanent disability, especially among infants and children. Emerging viral diseases such as those due to HIV, ebolavirus and hantavirus, appear regularly. Now that antibiotics effectively control most bacterial infections, viral infections pose a relatively greater and less controlled threat to human health. Some data suggest that the already broad gam.ut of established viral diseases soon may be expanded to include other serious human ailments such as juvenile diabetes, rheumatoid arthritis, various neurologic and immunologic disorders, and some tumors. Viruses can infect all forms of life (bacteria, plants, protozoa, fungi, insects, fish reptiles, birds, and mammals); however, this section covers only viruses capable of causing human infections. Like other microorganisms, viruses may have played a role in the natural selection of animal species. A documented example is the natural selection of rabbits resistant to virulent myxoma virus during several epidemics deliberately induced to control the rabbitpopulationin Austri;tlia. Indirect evidence suggests that the same selective role was played by smallpox virus in humans: Another possible, though unproved, mechanism by which viruses may affect evolution is by introducing viral genetic material into animal cells by mechanisms similar to those that govern gene transfer by bacteriophages. For example, genes from avirulent retrovirus integrated into genomes of chickens or mice produce resistance to reinfection by related, virulent retroviruses. The same. relationship may exist for human retroviruses, since human leukemia-causing retroviruses have been reported. -Viruses are small, s:ubcellular agents that are unable to multiply outside a host cell (intracellular, obligate parasitism). The assembled virus virion) is formed to include only one type of nucleic acid (RNA or DNA) and, in the simplest viruses, a protective protein coat. The nucleic add contains the genetic information necessary to program the synthetic machinery of the host cell for viral replication, The protein coat serves· two main functions: first, it protects the nucleic acid· from extracellular environmental insults such as nucleases; second, it permits attaclunent of the virion to the membrane of the host cell, the negative charge of which would repel a naked

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Text Book of Virology

. nucleic acid. Once the viral genome has penetrated and thereby infected the hostcell, virus replication mainly depends on host cell machinery for energy and synthetic requirements. The various virion components are synthesized separately within the cell and then assembled to form progeny particles. This assembly type of replication is unique

· to viruses and distinguishes them from all other small, obligate, intracellularparasites. The' basic structure of viruses may permit them to be simultaneouslyadaptable and selective. Many viral genomes are so adaptable that once· they havepenetrated the cell membrane under experimental conditions,viral.replication canoccur in almost any cell. On the other hand, intact viruses are so selective that mostvirions can infect only a limited range of cell types. This selectivity exists largelybecause penetration of the nucleic acid. usually requires a specific reaction for thecoat.to attach to the host cell membrane .and some specific intracellular components.Although somE;! viruses may establish some forms of silent infection of cells; theirmultiplication usually causes cell damage or q.eath; however, since viruses mustdepend on host survival for their owri survival, they tend to establish mild .infectionsin which death of the host is more an aberration than a regular outcome. Notableexceptions are HIV, ebolavirus, hantavirus and rabies".'irus.Viruses are distinct among microorganisms in. their extreme dependence on thehost cell. Since a virus must grow within a host cell, the virus must be viewedtogether with its host_in any consideration of pathogenesis, epidemiology,·hostdefenses, or therapy. The bilateral association between the virus and its host imposesspecific conditions for pathogenesis. For example,. rhinoviruses require atemperature not exceeding 34°C; this requirement restricts their growth to onlythose cells in the cool outer layer of the nasal mucosa, thereby preventing spread todeeper cells where temperatures are higher.The intracellular location of the virus often protects the virus against some of thehost's immune mechanisms; at the same time, this location makes the virus

. vulnerable because of its dependence on the host cell's synthetic machinery, whichmay be altered by even subtle physical and chemical changes produced by theviral infection (inflammation, fever, circulatory alterations, and interferon).Epidemiologic properties depend greatly on the characteristics of the virus-hostassociation. For example, some arthropod-borne viruses ,require aruu:row range oftemperature to multiply in insects; as a result, these viruses are found only undercertain seasonal.and geographic conditions. Other environmental conditionsdetermine the transmissibility of viruses in aerosols and in food.Viruses are difficult targets for chemotherapy because they replicate only withinhost cells, mainly utilizing many of the host cell's biosynthetic processf:!s. Thesimilarity of host-directed and virus-directed processes makes it difficult to findantiviral agen specific imouh to exert a greater effect on viral replication in

·2

Introduction to Virology

infected cells than on functions in uninfected host cells. It is becoming increasingly apparent, however, that each virus may have a few specific teps of rplication that may be used as. targets for highly selective, carefully aimed chemotherapeutic agents. Therefore, proper use of such drugs requires a thorough knowledge of the suitable targets, based on a correct diagnosis and a precise understanding of the replicative mechanisms for the offending virus. Knowledge of the pathogenetic mechanisms by which virus enters, spreads within, and exits from the body also is critical for correct diagnosis and treatment of disease and for prevention of spread in the environment. Effective treatment with antibody­containing immunoglobulin requires knowing when virus is susceptible to antibody (for example, during viremic spread) and when virus reaches target organs where

· antibody is less effective. Many successful vaccines have been based on knowledge· of pathogenesis and immune defehses. Comparable considerations governtreatment with interferon. Clearly, viral infections are among the most difficult and demanding problems aphysician must face: Unfortunately, some of these problems still lack satisfactory solutions, although tremendous progress has been made during the last several decades. Many aspects of medical virology are now understood, others are being clarified gradually, and many more are still obscure. Knowledge of the properties, of viruses and the relationships they establish with their hosts is crucial to successful investigation and clinical management of their pathologic processes. Our plan for conveying this knowledge is to present, first, concepts of viral structure,and then relate them to principles of viral muJtiplication. Together these concepts form the basis for understanding how viruses are classified, how they affect ells, and how their genetic system functions. These molecularand cellular mechanismsare combined with the concepts of immunology to explain viral pathogenesis, nonspecific defenses, persistent infections, epidemiology, evolution, and control. The important virus families are then discussed individually. Having studied the virology section, the reader should be able to use many principles of virology to explain individual manifestations of virus infection and the processes that bring them about.

3

Chapter·2

Structure and Classification

· of Viruses .

General Concepts

· Structure and Function

Viruses are small obligate intracellular parasites, which by definition contain eitli.era RNA or DNA genome . surrounded by a protective, virus-coded protein coat. Viruses may be viewed as mobile genetic elements, most probably of cellular originand characterized by a long co-evolution of virus and host. For propagation viruses depend on specialized host cells supplying the complex metabolic and biosynthetic machinery of eukaryotic or prokaryotic cells. A complete virus particle is called ·a virion. The main function of the virion is to deliver its DNA or RNA genome into the host cell so. that the genome can be expressed (transcribed and translated) by the host cell. The viral genome, often with associated basic proteins, is packagedinside a symmetric protein capsid. The nucleic acid-associated protein, called nucleoprotein, together with the genome, forms the nucleocapsid. • In enveloped viruses, the nucleocapsid is surrounded by a lipid bilayer derived from the modifiedhost cell membrane and studded with an outer layer of virus envelope glycoproteins. Classification of Viruses

Morphdlogy: Viruses are grouped on the basis of size and shape, chemicalcomposition and structure of the genome, and mode of replication: Helical morphology is seen in nucleocapsids of many filamentous and pleomorphic viruses. Helical nµcleocapsids consist of a helical array of capsid proteins (protomers)wrapped around a helical filament of nucleic acid. Icosahedral morphology is characteristic of the nucleocapsids of many "spherical" viruses. The number andarrangement of the capsomeres (morphologic subunits of the i'cosahedron) are useful

. in identification and classification. Many viruses also have ,an outer envelope. Chemical Composition and Mode of· Replication: The genome of a virus mayconsist of DNA or RNA, which may be single stranded (ss) or double strandd (ds), linear or circular. The entire genome may occupy either orie nucleic acidmolecule (monopartite genome) or several nucleic acid segments (multipartite genome). The different types of genome necessitate different replicationstrategies.

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Textbook Of Virology

Publisher : CBS Publications ISBN : 9788181894755 Author : Vinod Singh

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