Immune Checkpoints in Viral Latency

The dynamics of the relationship between the immune system and latent viruses are highly complex. Latent viruses not only avoid elimination by the host's primary immune response, they also remain with the host for life in the presence of strong acquired immunity, often exhibiting periodic reactivation and recurrence from the latent state. The continual battle between reemergent infectious virus and immunological memory cells provides an essential virus-host regulatory loop in latency. In this review, we speculate on the critical importance of immune interference mechanisms by viruses contributing to the regulatory loop in viral homeostasis of latency. Central to the notion of viral homeostasis, we further invoke the concept of threshold limits in naive and memory states of immunity to account for the failure of the host to completely eradicate these intracellular parasites.