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 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 β1 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).