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.