Secreted Immunomodulatory Viral Proteins as Novel Biotherapeutics

Abstract

Many viruses have learned to evade or subvert the host antiviral immune responses by encoding and expressing immunomodulatory proteins that protect the virus from attack by elements of the innate and acquired immune systems. Some of these viral anti-immune regulators are expressed as secreted proteins that engage specific host immune targets in the extracellular environment, where they exhibit potent anti-immune properties. We review here viral immunomodulatory proteins that have been tested as anti-inflammatory reagents in animal models of disease caused by excessive inflammation or hyperactivated immune pathways. The potential for such viral molecules for the development of novel drugs to treat immune-based or inflammatory disorders is discussed.

Myxoma virus in the European rabbit: interactions between the virus and its susceptible host

“…They functionally bind and inhibit extracellular host ligands which are intended to induce an inflammatory or antiviral response following virus infection [42]. On the contrary, virokines are normally secreted and are often similar to host immune ligands such as cytokines, or chemokines, but usually the viral versions are smaller or have alternative biological properties compared to the host ligands [54,64,90]. Examples of myxoma encoded secreted immunomodulatory proteins include the following: (1) M-T1, an inhibitor of CC-chemokines; (2) M-T2, a tumor necrosis factor receptor homolog; (3) M-T7, a homolog of the interferongamma receptor; (4) Serp-1, a secreted serine proteinase inhibitor; (5) myxoma growth factor, ligand for the erbB family of EGF receptors.…”

Viral IL-6 Blocks Neutrophil Infiltration during Acute Inflammation

“…A representative EMSA or immunoblot is shown, plus the average fold induction and SE calculated from densitometry analysis of three experiments, using cell isolates from different donors. (29). These strategies appear fundamentally designed to advance the cause of the virus; however, studies presented in this current communication show that HHV8-encoded vIL-6 has the capacity to influence the course of an acute inflammatory response.…”

Strategies that modulate inflammasomes—insights from host–pathogen interactions

“…Generally, the consequences of bacterial or viral modulation of inflammasome activities provide a more supportive environment for either the pathogen replication or subsequent dissemination. It is conceivable that future generations of inflammasome inhibitors could be patterned on the microbial modulators themselves, similar to how secreted anti-inflammatory regulators from viruses [69] have been co-opted to treat clinical diseases that are mediated by chronically dysregulated pro-inflammatory cascades. Whether the discovery of the inflammasome truly constitutes the "Rosetta stone" of innate immunity and inflammatory responses [25] will be determined by history.…”