Principles of Virology, Volume 1. Jane Flint

place to produce mRNA. Perhaps more pragmatically, the system simplifies comprehension of the extraordinary reproduction cycles of viruses.

      The Baltimore system omits the second universal function of viral genomes, to serve as a template for synthesis of progeny genomes. Nevertheless, there is also a finite number of nucleic acid-copying strategies, each with unique primer, template, and termination requirements. We shall combine this principle with that embodied in the Baltimore system to define seven strategies based on mRNA synthesis and genome replication. The Baltimore system has stood the test of time: despite the discovery of multitudes of viral genome sequences, they all fall into one of the seven classes.

      Replication and mRNA synthesis present no obvious challenges for most viruses with DNA genomes, as all cells use DNA-based mechanisms. In contrast, animal cells possess no known systems to copy viral RNA templates and to produce mRNA from them. For RNA viruses to propagate, their RNA genomes must, by definition, encode a nucleic acid polymerase.

Structure and Complexity of Viral Genomes

      Despite the simplicity of expression strategies, the composition and structures of viral genomes are far more varied than those seen in the entire archaeal, bacterial, or eukaryotic domains. Nearly every possible method for encoding information in nucleic acid can be found in viruses. Viral genomes can be

       DNA or RNA

       DNA with short segments of RNA

       DNA or RNA with covalently attached protein

       single-stranded (+) strand, (–) strand, or ambisense (Box 3.2)

       double stranded

       linear

       circular

       segmented

       gapped

      PRINCIPLES Genomes and Genetics

       The genomes of viruses range from the extraordinarily small (<2 kb) to the extraordinarily large (>2,500 kbp); the diversity in size likely provides advantages in the niches in which particular viruses exist.

       Viral genomes specify some, but never all, of the proteins needed to complete the viral reproductive cycle.

       That only seven viral genome replication strategies exist for all known viruses implies unity in viral diversity.

       Some genomes can enter the reproduction cycle upon entry into a target cell, whereas others require prior repair or synthesis of viral gene products before replication can proceed.

       Although the details of replication differ, all viruses with RNA genomes must encode either an RNA-dependent RNA polymerase to synthesize RNA from an RNA template or a reverse transcriptase to convert viral RNA to DNA.

       The information encoded in viral genomes is optimized by a variety of mechanisms; the smaller the genome, the greater the compression of genetic information.

       The genome sequence of a virus is at best a biological “parts list” and tells us little about how the virus interacts with its host.

       Technical advances allowing the introduction of mutations into any viral gene or genome sequence are responsible for much of what we know about viruses.

BOX 3.1

      BACKGROUND

       What information is encoded in a viral genome?

      Gene products and regulatory signals required for

       replication of the genome

       efficient expression of the genome

       assembly and packaging of the genome

       regulation and timing of the reproduction cycle

       modulation of host defenses

       spread to other cells and hosts

      Information not contained in viral genomes:

       genes encoding a complete protein synthesis machine (e.g., no ribosomal RNA and no ribosomal or translation proteins)

       genes encoding proteins of membrane biosynthesis

       telomeres (to maintain genomes) or centromeres (to ensure segregation of genomes)

       this list becomes shorter with each new edition of this textbook!

Figure 3.1 The Baltimore classification. All viruses must produce mRNA that can be translated by cellular ribosomes. This classification system traces the pathways from viral genomes to mRNA for the seven classes of viral genomes.

The seven strategies for expression and replication of viral genomes are illustrated in Fig. 3.2 to 3.8. In some cases, genomes can enter the replication cycle directly, but in others, genomes must first be repaired, and viral gene products that participate in the replication cycle must first be synthesized. Examples of specific viruses in each class are provided.

BOX 3.2

      TERMINOLOGY

       Important conventions: plus (+) and minus (–) strands

      mRNA is defined as the positive (+) strand, because it can be translated. A strand of DNA of the equivalent polarity is also designated as a (+) strand; i.e., if it were mRNA, it would be translated into protein.

      The RNA or DNA complement of the (+) strand is called the (–) strand. The (–) strand cannot be translated; it must first be copied to make the (+) strand. Ambisense RNA contains both (+) and (–) sequences.

      A color key for nucleic acids, proteins, membranes, cells, and more is located in the front of this book.

DNA Genomes

      The strategy of having DNA as a viral genome appears at first glance to be the ultimate in genetic efficiency: the host genetic system is based on DNA, so viral genome replication and expression could simply emulate the host system. While the replication of viral and cellular DNA genomes is fundamentally similar, the mechanistic details are varied because viral genomes are structurally diverse.

       Double-Stranded DNA (dsDNA) (Fig. 3.2)

      There are 38 families of viruses with dsDNA genomes. Those that include vertebrate viruses are the Adenoviridae, Alloherpesviridae, Asfarviridae, Herpesviridae, Papillomaviridae, Polyomaviridae, Iridoviridae, and Poxviridae. These genomes may be linear or circular. Genome replication and mRNA synthesis are accomplished by host or viral DNA-dependent DNA and RNA polymerases.

       Gapped DNA (Fig. 3.3)