A few DNA viruses use host-cell DNA polymerase to replicate their genome. Unfortunately for these viruses, DNA polymerase is expressed at high levels only during S phase of the cell cycle, and most cells that these viruses infect spend most of their time in G1 phase. Adenovirus has evolved a mechanism to drive the host cell into S phase, so that the cell produces large amounts of active DNA polymerase, which then replicates the viral genome; to accomplish this, the adenovirus genome also encodes proteins that inactivate both Rb (see Figure 17–61) and p53 (see Figure 17–62), two key suppressors of cell-cycle progression. As might be expected for any mechanism that encourages unregulated DNA replication, these viruses can promote, under some circumstances, the development of cancer. Other DNA viruses, including poxviruses and mimivirus, encode their own DNA and RNA polymerases, as well as some transcription regulators, allowing them to bypass usual host pathways and replicate outside the nucleus.
RNA viruses must always encode their own replication proteins because host cells lack polymerase enzymes that use RNA as a template. For RNA viruses with a single-stranded genome, the replication strategy depends on whether the RNA is a positive [+] strand, which contains translatable information like mRNA, or a complementary negative [–] strand. When the RNA is a positive [+] strand, the incoming viral genome is used to produce the viral RNA polymerase and viral proteins; the viral polymerase is then used to replicate the viral RNA and to generate mRNAs for the production of more viral proteins. For viruses with a negative [–] strand RNA genome (such as influenza and measles virus), an RNA polymerase enzyme is packaged as a structural protein of the incoming viral capsids.
Retroviruses such as HIV-1, which have a positive [+] strand RNA genome, are a special class of RNA virus because they carry with them a viral reverse transcriptase enzyme. After entry to the host cell, the reverse transcriptase uses the viral RNA genome as a template to synthesize a double-stranded DNA copy of the viral genome, which enters into the nucleus and integrates into the host cell’s chromosomes (see Figure 5–62). It is later transcribed by the cell’s DNA-dependent RNA polymerase to produce viral genomes and proteins.
The complexity and specificity of the interplay between pathogens and their host cells might suggest that virulence would be difficult to acquire by random mutation. Yet, new pathogens are constantly emerging, and old pathogens are constantly changing in ways that make familiar infections more difficult to prevent or treat. Pathogens have two advantages that enable them to evolve rapidly. First, they replicate very quickly, providing a great deal of material for natural selection to work with. Whereas humans and chimpanzees have acquired a 2% difference in genome sequences over about 8 million years of divergent evolution, poliovirus
Figure 23–29 Molecular mechanisms for actin nucleation by various bacterial pathogens. Listeria monocytogenes and Shigella flexneri induce actin nucleation by recruiting and activating the host Arp 2/3 complex (see Figure 16–16), although each uses a different recruitment strategy:
L. monocytogenes expresses a surface protein, ActA, that directly binds  to and activates the Arp 2/3 complex;
S. flexneri expresses a surface protein,  IcsA (unrelated to ActA), that recruits the host protein N-WASp, which in turn recruits the Arp 2/3 complex, along with other host proteins, including WIP (WASp-interacting protein). Rickettsia rickettsii uses an entirely different strategy; it expresses a surface protein, Sca2, that directly nucleates actin polymerization by mimicking the activity of host formin proteins.