Stealth Strategies Research Articles

Frontal and stealth attack strategies in microbial pathogenesis.

Interactions between microbes and human hosts can range from a benign, even symbiotic collaboration to a competition that may turn fatal--resulting in death of the host, the microbe or both. Despite advances that have been made over the past decades in understanding microbial pathogens, more people worldwide still die every year from infectious disease than from any other cause. This highlights the relevance of continuing to probe the mechanisms used by microorganisms to cause disease, and emphasizes the need for new model systems to advance our understanding of host-pathogen interactions.

Viral interference with apoptosis

Viruses have exploited a fascinating array of mechanisms to inhibit programed cell death. Different viruses tamper with cell suicide pathways by terminating cell death receptor signalling, mimicking cellular Bc1-2 functions, encoding protease inhibitors and other tactics. These stealth strategies are likely to be essential for the preservation of some viruses as it appears nearly impossible for a virus to enter a cell and set up housekeeping without setting off the alarm system that triggers activation of the cell death pathway. Thus, many viruses have developed strategies to subvert the cellular selfdestruct mechanisms, thereby providing suitable environments for long-term persistence, the establishment of latency or for progeny virus production. Investigation of these viral strategies has significantly advanced our knowledge of cellular death pathways and has impacted on our understanding of viral pathogenesis.

Interference with antigen processing by viruses

Viruses that establish persistent infections in their host, such as herpesviruses, adenoviruses or HIV, express proteins designed to pre-empt or evade recognition and elimination by MHC class I restricted CD8 + T lymphocytes. Notable discoveries during the annual period of review have demonstrated that, in principle, each single step within the MHC class I pathway of antigen processing and presentation is fair game for manipulation by viral functions. The viral factors that are natural inhibitors of this pathway have been instrumental for the elucidation of the distinct molecular mechanisms that are exploited by viruses. The viral stealth strategies that downregulate MHC class I protein surface expression may lead, however, to a higher susceptibility of virus-infected cells to natural killer cell activity. Strikingly, there is evidence that some viruses counteract increased natural killer cell recognition by expressing viral MHC class I homologues that function as surrogate inhibitors of natural killer cell activity.