The SCHOOL of nature: IV. Learning from viruses.

Abstract

During the co-evolution of viruses and their hosts, the latter have equipped themselves with an elaborate immune system to defend themselves from the invading viruses. In order to establish a successful infection, replicate and persist in the host, viruses have evolved numerous strategies to counter and evade host antiviral immune responses as well as exploit them for productive viral replication. These strategies include those that modulate signaling mediated by cell surface receptors. Despite tremendous advancement in recent years, the exact molecular mechanisms underlying these critical points in viral pathogenesis remain unknown. In this work, based on a novel platform of receptor signaling, the Signaling Chain HOmoOLigomerization (SCHOOL) platform, I suggest specific mechanisms used by different viruses such as human immunodeficiency virus (HIV), cytomegalovirus (CMV), severe acute respiratory syndrome coronavirus, human herpesvirus 6 and others, to modulate receptor signaling. I also use the example of HIV and CMV to illustrate how two unrelated enveloped viruses use a similar SCHOOL mechanism to modulate the host immune response mediated by two functionally different receptors: T cell antigen receptor and natural killer cell receptor, NKp30. This suggests that it is very likely that similar general mechanisms can be or are used by other viral and possibly non-viral pathogens. Learning from viruses how to target cell surface receptors not only helps us understand viral strategies to escape from the host immune surveillance, but also provides novel avenues in rational drug design and the development of new therapies for immune disorders.