Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

1288 Chapter 23: Pathogens and Infection
Figure 23–28 The actin-based movement of bacterial pathogens
within and between host cells. (A) Following invasion, bacterial pathogens
such as Listeria monocytogenes, Shigella flexneri, Rickettsia rickettsii, and
Burkholderia pseudomallei induce the assembly of actin-rich tails in the
host-cell cytoplasm, which drives rapid bacterial movement. For most of
these pathogens, the moving bacteria collide with the host-cell plasma
membrane to form membrane-covered protrusions, which are engulfed by
neighboring cells—spreading the infection from cell to cell. In contrast, for
B. pseudomallei, collision with the plasma membrane promotes cell–cell
fusion, creating a conduit through which bacteria can invade neighboring
cells (Movie 23.7).
free bacterium
phagocytosis
by zipper
mechanism
host cell
bacterial
escape from
phagosome
The molecular mechanisms of pathogen-induced actin assembly differ for the
different pathogens, suggesting that they evolved independently (Figure 23–29).
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 trans cription
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 hostcell
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).
actin
nucleation
actin tail assembly
motile
bacteria
engulfment by
neighboring host cell
cell
fusion
protrusion formation
MBoC6 m24.37/23.28