L. monocytogenes and baculovirus produce proteins that directly bind to and activate the Arp 2/3 complex to initiate the formation of an actin tail and movement (see Figure 16–16). S. flexneri produces an unrelated surface protein that binds to and activates N-WASp, which then activates the Arp 2/3 complex. Rickettsia species produce a protein that directly polymerizes actin by mimicking the function of host formin proteins (see Figure 16–17).
Many viral pathogens rely primarily on microtubule-dependent motor proteins rather than actin polymerization to move within the host-cell cytosol. Viruses that infect neurons, such as the neurotropic alpha herpesviruses, which include the virus that causes chickenpox, provide important examples. The virus enters sensory neurons at the tips of their axons, and microtubule-based retrograde “backward” axonal transport carries the nucleocapsids down the axon to the nucleus. The transport is mediated by attachment of viral capsid proteins to the motor protein dynein (see Figure 16–58). After replication and assembly in the nucleus, the enveloped virions are then carried by antegrade “forward” axonal transport along microtubules to the axon tips, with the transport being mediated by the attachment of a different viral capsid protein to a kinesin motor protein (see Figure 16–56). A large number of viruses associate with either dynein or kinesin motor proteins to move along microtubules at some stage in their replication. As microtubules serve as oriented tracks for vesicular transport in eukaryotic cells, it is not surprising that many viruses have independently evolved the ability to exploit them for their own transport.
Viruses Can Take Over the Metabolism of the Host Cell
Viruses use basic host cell machinery for most aspects of their reproduction: they depend on host-cell ribosomes to produce their proteins, and most use host-cell DNA and RNA polymerases for their own replication and transcription. Many viruses encode proteins that modify the host transcription or translation apparatus to favor the synthesis of viral RNAs and proteins over those of the host cell, shifting the synthetic capacity of the cell toward the production of new virus particles. Poliovirus, for example, encodes a protease that specifically cleaves the TATA-binding component of TFIID (see Figure 6–17), shutting off transcription of most of the host cell’s protein-coding genes. Influenza virus produces a protein that blocks both the splicing and the polyadenylation of host-cell RNA transcripts, preventing their export into the cytosol (see Figure 6–38).
Viruses also alter translation by the host. Translation initiation for most host-cell mRNAs depends on recognition of their 5ʹ cap by translation initiation factors (see Figure 6–70). This initiation process is often inhibited during viral infection, so that the host-cell ribosomes can be used more efficiently for the synthesis of viral proteins. Some viral genomes encode endonucleases that cleave off the 5ʹ cap from host-cell mRNAs; some go even further by using the liberated 5ʹ caps as primers to synthesize viral mRNAs, a process called cap snatching. Several other viral RNA genomes encode proteases that cleave certain translation initiation factors; these viruses rely on 5ʹ cap-independent translation of their own RNA, using internal ribosome entry sites (IRESs) (see Figure 7–68).