13. Monkeypox virus and mechanisms of immune evasion
Monkeypox virus (MPXV) has sequence similarities with vaccinia virus (VACV) and uses a variety of strategies to avoid detection by the immune system. The MPXV F3 protein and the VACV E3 protein are homologous, indicating a possible functional relationship. MPXV suppresses the antiviral immune response more effectively than a VACV mutant missing the N-terminal region of its E3 homolog.This suggests that MPXV may prevent symptoms caused by its E3 homolog’s lack of the N-terminal region. MPXV cannot downregulate MHC Class I; instead, it employs a method to prevent CD4+ and CD8+ T-cell activation upon interaction with MPXV-infected cells.
By suppressing local T-cell responses, MPXV can evade the immune system while maintaining a viral reservoir. MPXV-encoded immunomodulators play a critical role in blocking antiviral T-cell responses, which are activated by the host. Neutralizing antibodies are crucial for protection against severe MPXV infections, while memory T-cells alone do not provide sufficient protection. The spread of MPXV relies on interactions with circulating monocytes, which may protect the virus from humoral immune responses. Macrophages and other immune cells may also aid in the spread of MPXV. Understanding the immune evasion mechanisms of MPXV and the interactions between various orthopoxviruses, such as VACV, is important for studying immunity to monkeypox and developing effective preventive measures like vaccinations.