Virology – an overview | ScienceDirect Topics

Virology has come a long way from the days of ‘unfilterable agents’, of Ivanoviskii’s and Beijerinck’s Tobacco Mosaic virus, to Hershey and Chase’s experiments leading to the discovery that genes are composed of DNA (Creager, 2002;

From: Methods in Microbiology, 2015

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Richard Allen WhiteIII, … Randall T. Hayden, in Methods in Microbiology, 2015


In the past 25 years, virology has had major technology breakthroughs stemming first from the introduction of nucleic acid amplification testing, but more recently from the use of next-generation sequencing, digital PCR, and the possibility of single virion genomics. These technologies have and will improve diagnosis and disease state monitoring in clinical settings, aid in environmental monitoring, and reveal the vast genetic potential of viruses. Using the principle of limiting dilution, digital PCR amplifies single molecules of DNA in highly partitioned endpoint reactions and reads each of those reactions as either positive or negative based on the presence or absence of target fluorophore. In this review, digital PCR will be highlighted along with current studies, advantages/disadvantages, and future perspectives with regard to digital PCR, viral load testing, and the possibility of single virion genomics.

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Peter C. Doherty, in Fenner and White’s Medical Virology (Fifth Edition), 2017

Basic virology has, of course, been well served by the many revisions of Bernie Fields’ (1938–1995) exhaustive text and, following the example set by Field’s Virology, the fifth edition will appear as Fenner and White’s Medical Virology. It is a fitting tribute. Taken together, the original authors, and those responsible for this latest version, have variously been active and publishing on one or the other aspect of virus-induced disease and/or pathology since 1948: and the virology lineage goes back even further!

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In Viral Pathogenesis (Third Edition), 2016

Virology, together with all of biomedical sciences, is undergoing a revolution that can be encapsulated as a transition from reductionism to systems biology. This third edition of Viral Pathogenesis reflects this paradigm shift and the new perspective it brings to the field. Accordingly, this edition is organized in four different parts: (I) History and essentials of viral pathogenesis; (II) Systems-level approaches to viral pathogenesis; (III) Emergence and control of viral infections; and (IV) Past and future. Part I sets forth our knowledge based on long-established methods in pathology, virology, and adaptive immunity. This section provides the background for the rest of the book, which focuses on current and future methods and discoveries in viral pathogenesis.

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Kunihiro Tsukasaki, … Kensei Tobinai, in Abeloff’s Clinical Oncology (Fifth Edition), 2014

Virology and Pathogenesis

HTLV-I is reverse-transcribed into DNA and randomly integrated into the host cell.

The HTLV-I genome encodes two unique regulatory proteins—Tax and Rex—responsible for viral expression and cellular transformation. Tax trans-activates viral and cellular genes that could be involved in the pathogenesis of ATL. HTLV-I basic leucine zipper (HTLV-I bZIP; HBZ) is an antisense transcript of HTLV-I, is steadily expressed in ATL cells, and interacts with several host genes and suppresses the activity of Tax.

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Ronald B. Turner, in Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases (Eighth Edition), 2015

Virology and Epidemiology

Rhinoviruses are unenveloped RNA viruses in the family Picornaviridae.

One-hundred one serotypes have been detected, now divided into two phylogenetic species (human rhinovirus [HRV]-A and HRV-B); a third species, HRV-C, also exists.

Rhinoviruses are among the most common pathogens of man, with an incidence of 0.5 infections per year in adults and 2 infections per year in children.

Infections occur year-round, with seasonal peaks in the spring and fall in temperate climates.


The common cold is the characteristic clinical manifestation.

Exacerbations of asthma in children are frequently associated with rhinovirus infection.

Rhinoviruses may cause bronchiolitis in young children.

Specific virologic diagnosis is best accomplished with polymerase chain reaction but is rarely useful for patient management.


Despite multiple studies, no specific antiviral therapy has been established.


There is no proven intervention to prevent rhinovirus infection.

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Paul S. McNamara, H. Rogier Van Doorn, in Manson’s Tropical Infectious Diseases (Twenty-third Edition), 2014


Virology and clinical textbooks and virtually all web-based information sources describe the 99 serotypes of human rhinovirus (HRVs) as the most frequent cause of the common cold, in both the developed and the developing world. Although the common cold is considered a trivial illness, it is an important disease worldwide in terms of morbidity and economic impact.

In addition to causing the common cold, there is now convincing evidence that HRVs play a significant role in causing lower respiratory symptoms. HRVs can replicate in the lower airways and do appear to play a critical role in causing exacerbations of asthma and other chronic lung diseases. They can also drive the infant immune system towards the asthmatic phenotype, and cause episodes of bronchiolitis and pneumonia that require hospitalization.15

Until a few years ago, only two groups of HRVs (A and B) were recognized, but sequencing of HRVs led to the discovery of a third species (HRV-C) in 2006, with distinct structural, biological and possibly also clinical features.16,17

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Jennifer Louten, in Essential Human Virology, 2016


Virology is the study of viruses. The first viruses were discovered in 1898 and were identified by their ability to pass through filters that were too small to allow the passage of bacteria. Since that time, scientists have been studying viruses to better understand how to prevent epidemics and pandemics, and research on viruses has revealed an abundance of information on how living systems work. Viruses are the most abundant biological entities on Earth and infect all living things, and yet they are not considered to be alive. They share several characteristics with living organisms, but are unable to reproduce independently and maintain metabolic activities. In addition, they do not undergo cell division, like living organisms do, but assemble newly made components from scratch after gaining entry into a cell and its machinery. Viruses appeared around the same time that life began on Earth, but their origin is a much debated issue. The precellular hypothesis proposes that viruses existed before or alongside cells, whereas the escape hypothesis suggests that viruses were once components of living cells. The regressive hypothesis proposes that viruses were once living intracellular parasites that lost their ability to reproduce independently.

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A.E. Gorbalenya, … S. Siddell, in Reference Module in Biomedical Sciences, 2019

A Short History of Virology From the Perspective of Virus Taxonomy

Virology emerged as a science at the end of the 19th century as the study of minuscule agents responsible for plant and animal infectious diseases. Amongst the first viruses discovered were tobacco mosaic virus, foot and mouth disease virus and yellow fever virus (reviewed in Oldstone, 2014). About 30 years later, Rivers (Rivers, 1927) was able to list about three dozen diseases that were thought to be caused by viruses. Accordingly, at this time, mainly eukaryotic viruses were grouped together, essentially based on visual symptoms of disease and their modes of transmission. This classification predated any formal virus taxonomy but may still be regarded as its first phase. Subsequently, with the development of the electron microscope in the late 1930s, viruses, and in particular bacteriophages (Luria et al., 1943), were recognized as particles, and not long afterward nucleic acid and proteins were firmly established as components of small animal and plant viruses (Crick and Watson, 1956; Schaffer and Schwerdt, 1956). The introduction of cultured cells for the in vitro propagation of eukaryotic viruses (Enders et al., 1949) accelerated the pace of virus discovery and the need to classify and name groups of viruses became ever greater. At this point, the emphasis changed to a classification based upon virion morphology, the biology and genetics of viruses, and the physio-chemical properties of virus components. This might be looked upon as the second phase of virus classification. The later stages of this phase coincided with the foundation of the ICTV; spearheaded by leading virologists including Lwoff, Andrewes, and Wildy, and supported by the wider virology community (reviewed in Adams et al., 2017a).

In a subsequent third phase, virus taxonomy was increasingly dominated by information relating to the genome organization and replication strategies of viruses, at a time when virus particles were recognized as just one stage of the complex virus life cycle. With the application of first-generation methods of nucleic acid sequencing (Fiers et al., 1976), the volume of sequence information increased significantly, and sequence comparison and phylogenetic relationships were introduced (reviewed in Goldbach, 1986; Strauss and Strauss, 1988; Shukla and Ward, 1988) and became more important in taxonomy, although they were still mostly considered alongside other phenotypic characters (Francki et al., 1991). Finally, in the first two decades of the 21st century, this situation has again changed dramatically, with the introduction of affordable, extremely sensitive, and high-throughput sequencing technologies (Radford et al., 2012). This has led to the discovery of a multitude of novel viruses, the overwhelming majority of which are only recognized from their genomic information (reviewed in Zhang et al., 2019). The classification of viruses based on their genome sequence alone may be considered as the fourth and ongoing phase of virus taxonomy.

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Thomas C. Mettenleiter, in Advances in Virus Research, 2017

2 The First “Virus Hunters”

Virology started with a technological breakthrough, the development of porcelain and kieselgur (diatomacious earth) filters for sterilization of bacteria-containing material (reviewed in Mudd, 1928). Charles Edouard Chamberland (1851–1908) introduced his porcelain filters in 1884 working together with Louis Pasteur (Chamberland, 1884). These filters were produced in graded porosities from L1 (most coarse) to L13 (finest). Kieselgur filters which use a similar principle were invented and marketed by Wilhelm Berkefeld (1836–1897). A particularly fine porcelain filter had been developed by Shibasaburo Kitasato (1853–1931) for his studies, together with Robert Koch, on the tetanus toxin (Kitasato, 1891).

It was the Russian scientist Dimitri Iwanowski (1864–1920) who first analyzed the causative agent of tobacco mosaic disease by using these newly developed filters. He demonstrated that the agent causing this disease which had been shown to be infectious by Adolf Mayer (1843–1942), a German chemist working in Wageningen in the Netherlands (Mayer, 1886), passed through the bacteria-tight filters (Iwanowski, 1892). Thus, he first described “filterability” as a hallmark of the agent (Lvov, 1993). However, until his death he did not realize that he actually discovered a new world of pathogens but rather believed conservatively that filterability does not reflect a novel class of pathogens but simply considered the “filterable” agent of tobacco mosaic disease as a different, smaller form of bacteria. Thus, he was unable to grasp the fundamental change in concept his filtration experiments were indicative for.

The Dutch scientist Martinus Wilhelmus Beijerinck (1851–1931) also studied tobacco mosaic disease and was interested in identification of the causative agent. Apparently unaware of the previous work by Iwanowski, he essentially repeated his experiments with the same results, i.e., unhindered passage of the agent through Chamberland filters. In contrast to Iwanowski, however, Beijerinck understood that he discovered something novel, not resembling any of the known biological entities. He coined the term “contagium vivum fluidum” to describe this novel biological principle, which can be translated into “infectious liquid” (Beijerinck, 1898). He used this new term prominently in the title of his seminal publication highlighting the importance he attributed to this finding. Contagium vivum fluidum was used as opposed to contagium vivum fixum, which would indicate a particulate, corpuscular agent.

However, viruses are clearly no “infectious liquids” and that they are in fact ultrafilterable, but particulate was correctly observed for the first time by Friedrich Loeffler (1852–1915) (Fig. 1) working with Paul Frosch (1860–1928) on the agent causing foot-and-mouth disease in cloven-hoofed animals using a combination of Chamberland and the newly developed fine-grain Kitasato filters (Horzinek, 1995). The latter technological breakthrough was available to them since Shibasaburo Kitasato who worked in the laboratory of Robert Koch was familiar with the research of Loeffler and Frosch (both also former and present coworkers of Koch). Thus, technology was instrumental in defining this new class of infectious agents and Loeffler and Frosch proved its filterability, in vivo replication and corpuscular nature in their seminal 1898 “Third Report to the Prussian Minister of Culture,” dated January 8 (published on February 10 in the Deutsche Medizinische Wochenschrift and on March 10 in the Zentralblatt für Bakteriologie). It is interesting that Loeffler and Frosch also went further and hypothesized that this new concept might also apply to other infectious diseases caused by hitherto unknown microbes. They listed variola, cowpox, scarlet fever, measles, spotted typhus, and rinderpest as presumably being caused by filterable viruses (Loeffler and Frosch, 1898). Retrospectively, they were correct in four of the six examples but, more importantly, this testifies to Loeffler and Frosch’s recognition that a new class of infectious agents had indeed been found.

Fig. 1. Friedrich Loeffler (left) and Robert Koch, ca. 1880.

In summary, Beijerinck, in contrast to Iwanowski, was clearly aware that he had come across a change in concept, i.e., filterable novel infectious agents (in this context he first used the latin term “virus”), and has to be credited by the notion that “the contagion, to reproduce itself, must be incorporated into the living cytoplasm of the cell, into whose multiplication, it is, as it were, passively drawn” (Horzinek, 1995). However, his contagium vivum fluidum did not reflect the nature of the novel “virus.” Thus, Witz (1998) and Van Regenmortel (2010) summarize the available evidence to conclude that Loeffler and Frosch’s interpretation of their filtration experiments “came much closer to the modern concept of a virus than anybody else at the time” (Witz, 1998) and “so they should be acknowledged as the founders of virology” (Van Regenmortel, 2010) which has found support more recently also by Murphy (2016). Interestingly, neither Loeffler nor Frosch followed this up by more detailed studies on the nature of this agent. They were only interested in finding a prevention or cure for foot-and-mouth disease (Loeffler, 1898) with only limited success. Their serum therapy was costly and unreliable and was actually discouraged from being used (Fröhner, 1912).

Unfortunately and incorrectly, this conceptual leap which actually led to the foundation of a new discipline, virology, is still not universely attributed to Loeffler and Frosch but rather to Beijerinck or even Iwanowski (see Bos, 1995; Enquist and Racaniello, 2013; Lvov, 1993; Wilkinson, 2001).

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R.M. Goulter-Thorsen, L-A Jaykus, in Encyclopedia of Food Safety, 2014


Food virology is a relatively young field, at least from the perspective of food safety. The development of molecular techniques during the 1990s, in combination with increased epidemiological surveillance, have raised awareness of the importance of viruses to foodborne illness. Although methodological advancements have been made, much still remains unknown. The lack of a culture system for HuNoV is probably the single most important limiting factor to studying and controlling these viruses. With availability of such a method, or in its absence, availability of better cultivable surrogates or more sensitive detection methods for complex sample matrices, scientists would be able to tackle the challenges associated with trying to control foodborne viruses. Likewise, the availability of routine clinical assays would result in greater awareness of these diseases and improvements in reporting and epidemiological surveillance. The field of food virology is set to grow rapidly in the coming years as scientists tackle these problems with the aid of developing technologies.

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