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.
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.
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)
Members of two virus families, Caulimoviridae and He- padnaviridae, have a gapped DNA genome. The Hepadnaviridae include viruses that infect vertebrates. As the gapped DNA genome is partially double stranded, the gaps must be filled to produce perfect duplexes. This repair process must precede mRNA synthesis because the host RNA polymerase can transcribe only fully dsDNA. The unusual gapped DNA genome is produced from an RNA template by a virus-encoded enzyme, reverse transcriptase.
Single-Stranded DNA (ssDNA) (Fig. 3.4)
Thirteen families of viruses containing ssDNA genomes have been recognized; the families Anelloviridae, Circoviridae, Genomoviridae, and Parvoviridae include viruses that infect vertebrates. ssDNA must be copied into mRNA before proteins can be produced. However, RNA can be made only from a dsDNA template, whatever the sense of the ssDNA. Consequently, DNA synthesis must precede mRNA production in the replication cycles of these viruses. All synthesis of viral DNA is catalyzed by cellular DNA polymerases.
Figure 3.2 Structure and expression of viral double-stranded DNA genomes. (A) Synthesis of genomes, mRNA (shown as green line in yellow box), and protein (shown as brown line). The icon represents a polyomavirus particle. (B to E) Genome configurations. Ori, origin of replication; ITR, inverted terminal repeat; TP, terminal protein; L, long region; S, short region; UL and US, long and short unique regions; IRL, internal repeat
