E3116k

Bcl-2

Procaspase

FIGURE 8.23 Adenoviruses have been shown to both induce apoptosis (blue arrows and text) and to encode factors that inhibit apoptosis (red symbols and text).These moieties interfere with "killing via receptor" and with the p53 mediated pathway of apoptosis. [Drawn from data in Chinnadurai (1998).]

multiple products that oppose apoptosis and that many of these proteins appear be multifunctional. This illustrates the importance of controlling the apoptotic pathway after infection by these viruses. It is interesting that the adenoviruses are so efficient at suppressing apoptosis that they encode another protein, the adenovirus death protein, which leads to cell death and release of virus. This protein, which is produced only late after infection, may simply allow apop-tosis to proceed, or the protein may initiate some other pathway that results in the death of the cell.

Viral Counterdefenses against Cytokines and Chemokines

The cytokines and chemokines are powerful regulators of both innate and adaptive immune defenses. Because of the importance of these agents in the regulation of the immune response, and because of their potential effective ness againt viral infection, many viruses have devised methods to disrupt their activities. These include the encoding of homologs or analogs of cytokines and chemokines or of their receptors. Some of these were acquired from the host at some time in the past and modified to meet the purposes of the virus, whereas others are viral products that have evolved to interact with the cytokine system. Because the networks of cytokine and chemokine interactions are complex, the pathways by which the viral products exert their effects are often poorly understood. It is in the interest of the virus to divert the immune responses in directions that not only favor virus growth in the present host but also the persistence of the virus in nature. These two are often antagonistic, and compromises are required. Viruses also produce products that defeat specific aspects of the innate response induced by cytokines. Of these, products that evade the antiviral state induced by IFN are among the best understood. A partial listing of strategies used by some viruses to modulate cytokine activities is given in Table 8.9.

TABLE 8.9 Virus Manipulation of Cytokine Signaling

Virus family

Virus

Cellular target or homolog

Viral factor

Mode of action

Herpesviridae

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