IE3: The Viral Sensation

Abstract

Herpesviruses are ubiquitous DNA viruses that have been detected in every human population tested. These viruses have left their mark across the animal kingdom and are highly species-specific. Herpesviruses have the ability to enter a latent state and reactivate under certain conditions, allowing them to persist in their host for life. While typically asymptomatic, infection with these viruses can cause severe disease in immunocompromised individuals, leading to increased morbidity and mortality. These viruses share a similar structure and lytic replication cycle, during which proteins are expressed in a sequential order to facilitate replication. Of the animal models used for cytomegalovirus (CMV) studies, murine cytomegalovirus (MCMV) is the most well-characterized and is ideal for studying both viral biology and pathogenesis. Importantly, MCMV is specific to mice and does not infect humans, making it a safe and effective model for research without posing any risk to human health. MCMV has been crucial for investigating host cellular responses, including necroptosis, a virally-induced programmed cell death response. This model has helped map the necroptosis pathway and identified viral inhibitors that can regulate this process. The use of a pronecroptotic M45mutRHIM virus has provided valuable insights into the mechanisms essential for necroptosis. IE3 is an immediate early protein that plays an essential role in the regulation of viral genes and has been identified as a key viral protein for inducing necroptosis. This review discusses the omnipresence and species-specific nature of herpesviruses, their life cycle, seroprevalence, the severe diseases they can cause in immunocompromised individuals, and underlines the importance of MCMV as a model for studying viral biology and pathogenesis, emphasizing the significance of IE3 in MCMV pathogenesis.