Orthopoxvirus immune evasion proteins (OVP-IEPs)

Orthopoxviruses, including Variola (smallpox) and Monkeypox (Mpox) viruses, encode a diverse suite of immune evasion proteins that are critical for pathogenesis and viral persistence. These proteins function by neutralizing host immune signaling through several mechanisms: secreting soluble homologs of cytokine and chemokine receptors (e.g., B8R for IFN-gamma and B15R for IL-1beta) to act as decoys, and producing intracellular inhibitors like E3L and K3L that block the protein kinase R (PKR) and interferon-induced antiviral pathways (Stanford et al., 2007, J Gen Virol). Additionally, these viruses produce complement control proteins (e.g., VCP) and serpins to inhibit inflammatory cascades and apoptosis (Seet et al., 2003, Annu Rev Immunol). While these proteins are essential for the virus to overcome the host's innate defenses, they also represent potential therapeutic targets for small-molecule inhibitors or monoclonal antibodies. Currently, clinical management of orthopoxvirus infections primarily relies on drugs like Tecovirimat, which targets the F13L (VP37) protein to prevent viral egress, and Brincidofovir, which inhibits DNA polymerase (FDA, 2018, TPOXX Label). Research into specifically targeting the evasion proteins themselves aims to restore the host's natural ability to clear the infection and reduce viral virulence.

Other names

Poxvirus immunomodulatory proteinsOrthopoxvirus virulence factorsVaccinia virus immune evasion proteinsPoxvirus cytokine decoysViral complement control proteins

Inhibition of viral phospholipase (F13L/VP37) to prevent viral egress and spread; inhibition of viral DNA polymerase to arrest genome replication; experimental strategies aim to neutralize viral cytokine decoys or restore host PKR and interferon pathways.