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

CELL BIOLOGY OF INFECTION
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pumped into the early endosome also has another effect; it enters the influenza
virion through an ion channel in the viral envelope and triggers changes in the
viral capsid. These priming steps allow the capsids to disassemble once released
into the cytosol after virus fusion with the late endosomal membrane.
Nonenveloped viruses use different strategies to enter host cells—strategies
that do not rely on membrane fusion. Poliovirus, which causes poliomyelitis, binds
to a cell-surface receptor, triggering both receptor-mediated endocytosis (see Figure
13–52) and a conformational change in the viral particle. The conformational
change exposes a hydrophobic projection on one of the capsid proteins, which
inserts into the endosomal membrane to form a pore. The viral RNA genome then
enters the cytosol through the pore, leaving the capsid in the endosome (Figure
23–18C). Other nonenveloped viruses such as adenovirus disrupt the endosomal
membrane after they are taken up by receptor-mediated endocytosis. One of the
proteins released from the capsid lyses the endosomal membrane, releasing the
remainder of the virus into the cytosol. During endosomal trafficking and subsequent
transport within the cytosol, adenoviruses undergo multiple uncoating
steps, which sequentially remove structural proteins and ready the virus particles
to release their DNA into the nucleus through nuclear pore complexes (Figure
23–18D).
Bacteria Enter Host Cells by Phagocytosis
Bacteria are much larger than viruses—too large to be taken up either through
pores or by receptor-mediated endocytosis. Instead, they enter host cells by
phagocytosis, which is a normal function of phagocytes such as neutrophils, macrophages,
and dendritic cells (discussed in Chapter 24). These phagocytes patrol
the tissues of the body and ingest and destroy microbes; however, some intracellular
bacterial pathogens such as M. tuberculosis use this to their advantage and
have evolved to survive and multiply inside macrophages.
Some bacterial pathogens can invade host cells that are normally nonphagocytic.
One way they do so is by expressing an invasion protein that binds with high
affinity to a host-cell receptor, which is often a cell–cell or cell–matrix adhesion
protein (discussed in Chapter 19). For example, Yersinia pseudotuberculosis (a
bacterium that causes diarrhea and is a close relative of the plague bacterium
Y. pestis) expresses a protein called invasin that has an RGD motif that is similar
to fibronectin’s and likewise is recognized by host-cell β 1 integrins (see Figure
19–55). Listeria monocytogenes, which causes a rare but serious form of food
poisoning, invades host cells by expressing a protein that binds to the cell–cell
adhesion protein E-cadherin (see Figure 19–6). For both these bacterial species,
binding of the bacterial invasion proteins to the host cell adhesion proteins stimulates
signaling through members of the Rho family of small GTPases (discussed
in Chapter 16). This in turn activates proteins in the WASp family and the Arp 2/3
complex, leading to actin polymerization at the site of bacterial attachment. Actin
polymerization, together with the assembly of a clathrin coat (see Figure 13–6),
drives the advancement of the host cell’s plasma membrane over the adhesive
surface of the microbe, resulting in the phagocytosis of the bacterium—a process
known as the zipper mechanism of invasion (Figure 23–19A).
A second pathway by which bacteria can invade nonphagocytic cells is known
as the trigger mechanism (Figure 23–19B). It is used by various pathogens that
cause food poisoning, including Salmonella enterica, and it is initiated when the
bacterium injects a set of effector molecules into the host-cell cytosol through
a type III secretion system (see Figure 23–7). Some of these effector molecules
activate Rho family proteins, which in turn stimulate actin polymerization, as just
discussed. Other bacterial effector proteins interact with host-cell cytoskeletal
elements more directly, nucleating and stabilizing actin filaments and causing
the rearrangement of actin cross-linking proteins. The overall effect is to cause the
formation of localized ruffles on the surface of the host cell (Figure 23–19C and
D), which fold over and engulf the bacteria by a process that resembles macropinocytosis.
The appearance of cells being invaded by use of the trigger mechanism