Basic Virology. Martinez J. Hewlett

      While molecular principles of classification are of obvious importance to molecular biologists and molecular epidemiologists, other schemes have a significant amount of value to medical and public health professionals. The importance of insects in the spread of many viral diseases has led to many viruses being classified as arthropod‐borne viruses, or arboviruses. Interestingly, many of these viruses have general or specific similarities, although many arthropod‐borne viruses are not part of this classification. The relationships between two groups of RNA viruses that are classified as arboviruses are described in some detail in Part IV, Chapter 13.

      Viruses can also be classified by the nature of the diseases they cause, and a number of closely or distantly related viruses can cause diseases with similar features. For example, two herpesviruses, Epstein–Barr virus (EBV) and human cytomegalovirus (HCMV), cause infectious mononucleosis, and the exact cause of a given clinical case cannot be fully determined without virological tests. Of course, completely unrelated viruses can cause similar diseases too. Still, disease‐based classification systems are of value in choosing potential candidates for the etiology of a disease. A general grouping of some viruses by similarities of the diseases caused or organ systems infected was presented in Table 3.1.

THE VIROSPHERE

The ICTV published their tenth report in 2017. This report is available online (https://talk.ictvonline.org/ictv‐reports/ictv_online_report), and the current (2019) Master Species List database of viruses can be downloaded at the ICTV website (http://ictvonline.org). The current database contains 4958 different virus species arranged in 846 genera, 143 families, and 14 orders. They are listed by virus families in Table 5.1. While this is a notable achievement, it is not a complete one – the pace of discovery of new viruses and characterization of the genes they encode ensures that the number will change. Further, it is increasingly evident that the very nature of virus replication and association with their hosts leads to complications not found in classification schemes for cell‐based life. The rate of genetic change in viruses can be great due to the rapidity and frequency of genome replication with the associated opportunity for error. Viruses can also, however, exchange genetic elements with their hosts and any other genomes present in the same milieu in which the virus is replicating. Such an occurrence can lead to the creation of a new virus species in which some of its genes are derived from one lineage and some from another – clearly, its classification will be complicated.

Table 5.2 The Baltimore classification scheme for viruses.

RNA‐containing viruses

Single‐stranded RNA virusesPositive sense (virion RNA like cellular mRNA)NonenvelopedIcosahedralPicornavirusa (poliovirus,a hepatitis A virus,a rhinovirusa)CalicivirusesPlant virus relatives of picornavirusesMS2 bacteriophageaEnveloped Icosahedral Togavirusesa (rubella,a equine encephalitis, Sindbisa)Flavivirusesa (yellow fever,a dengue fever, Zika virus)Helical Coronavirusa (SARS‐CoV, MERS‐CoV)Positive sense but requires RNA to be converted to DNA via a virion‐associated enzyme (reverse transcriptase) Enveloped Retrovirusesa Oncornavirusesa (Rous sarcoma virus)Lentivirusesa (HIV)Negative‐sense RNA (opposite polarity to cellular mRNA, requires a virion‐associated enzyme to begin replication cycle) Enveloped Helical Mononegavirusesa (rabies,a vesicular stomatitis virus,a Ebola virusa)Segmented genome (orthomyxovirus–influenza,a bunyavirus‐hantavirus,a arenavirusa) Double‐stranded RNA virusesNonenveloped Icosahedral (reovirus,a rotavirusa) Single‐stranded DNA virusesNonenveloped Icosahedral Parvovirusesa (canine distemper, adeno‐associated virusa)Bacteriophage ΦX174a Double‐stranded DNA virusesNuclear replication Nonenveloped Icosahedral Small circular DNA genome (papovaviruses–SV40,a polyomaviruses,a papillomavirusesa)“Medium”‐sized, complex morphology, linear DNA (adenovirusa)Enveloped – nuclear replicating Icosahedral Herpesvirusesa (linear DNA)Hepadnavirusa (virion encapsidates RNA that is converted to DNA by reverse transcriptase)Cytoplasmic replication Icosahedral IridovirusComplex symmetry PoxvirusaBacterial viruses Icosahedral with tailT‐series bacteriophagesaBacteriophage λa

      ^a Discussed in text. MERS‐CoV: Middle East respiratory syndrome coronavirus; SARS‐CoV: severe acute respiratory syndrome coronavirus.

The best generalization that can be made concerning virus classification is that it depends on analysis of a number of features, and the importance of such features may vary depending upon the use being made of the classification. A classification scheme that combines the Baltimore basis along with the nature of the host and detailed genetic characterization of critical viral proteins can generate a global view of viruses as a virosphere, such as that shown in Figure 5.5.

Figure 5.5 The virosphere. Classification of a major portion of the currently known families of viruses (‐viridae) using criteria defined by the International Committee on Taxonomy of Viruses (ICTV). Major groupings are based on the nature of the viral genome and the nature of the host.

      The features of viruses discussed in this chapter provide the basis for this comprehensive classification scheme, but they are not complete – for example, diseases caused by viruses cannot be readily listed. Further, relationships between virus families will often transcend the nature of the host – this would require a third dimension to the scheme (appropriate to the concept of a sphere). Since the concept of species in biology has always been a problem, it is no surprise that relationships between viruses pose a number of specific and profound problems. For more distantly related groups, the problems grow. Still, throughout this confusion, virus families made up of related species or types are clear, and it is possible to group some major virus families into superfamilies – we will see that this can be done for the Herpesviridae and certain bacteriophages. As a rationalization, it is useful to consider virus families and larger groupings as polythetic – a group whose members always have several properties in common, although no single common attribute is present in all of its members. As a result, no single property can be used as a defining property of a polythetic group on the basis that it is universally present in all the members and absent in the members of other groups. For viruses, it is impossible to use any one discriminating character for distinguishing related groups and families, because of the inherent variability of the members.

THE HUMAN VIROME

      Recently, high‐throughput sequencing (Chapter 11) coupled with metagenetic analysis (Chapter 22) have expanded our understanding of the number and types of viruses that are a normal part of the flora of the human body. The so‐called human virome is in the process of being mapped for the blood, the gut, and various other locations that are a part of human anatomy, similar to work being done with bacterial species and the human microbiome. Since the techniques that lead to an understanding of the virome will be discussed later in this