Immune Evasion by Viruses


When a virus infects a host, a complex immune response develops to eliminate the invading pathogen. Viruses, in turn, have evolved a profusion of strategies to escape from the immune system. Mechanisms of viral evasion can be separated into those that occur at the cellular level and those that are important at the systemic level. Viruses can avoid detection by both innate and adaptive immune responses. Pattern recognition receptors in infected cells, interferons, dendritic cells, T cell receptors and antibodies are all targets of viral evasion proteins. Viruses can express proteins that directly interfere with host processes or mimic host proteins and compete to bind specific receptors. Pathogens are also able to directly deplete immune cells, and prevent their recruitment to the site of infection. In a state of latency, viruses remain dormant and undetectable in host cells. The diversity of these mechanisms has allowed us to dissect the immune system further and understand how viruses persist despite such a strong counterattack by the immune system.

Key Concepts:

  • Viruses have evolved a plethora of mechanisms to inhibit every step of the innate and adaptive immune responses.

  • Viruses avoid detection by pattern recognition receptors, T cell receptors and antibodies by modifying the ligands for these receptors.

  • Different viruses target every stage of antigen processing and presentation by MHC molecules, thus inhibiting recognition by T cells.

  • Interferons, cytokines and chemokines are mimicked or blocked by viral proteins to prevent the efficient development of an immune response.

  • Through repression of their replication, viruses are able to enter latency and remain dormant inside the cell, remaining undetectable.

Keywords: virus; immune evasion; escape; antigen presentation; cellular response MHC; immune response; antibodies; latency; interferons

Figure 1.

Interference with the MHC‐peptide presentation pathway. Viruses encode a plethora of proteins that disrupt this pathway at all levels. (1) Inhibition of MHC transcription. (2) Inhibition of proteasomal degradation. (3) TAP inhibition prevents peptide transport into the ER. (4) Tapasin inhibition prevents the interaction between the peptide and class I MHC protein. (5) MHC molecules are prevented from leaving the ER. (6) MHC molecules are targeted for proteasomal degradation. (7) Translocation of MHC molecules to the surface is disrupted.

Figure 2.

Physical shielding from the immune system. (1) Replication of Dengue virus occurs in ER‐derived structures called Vesicle Packets. (2) Viruses such as HIV‐1 are able to suppress viral protein transcription by inducing latency and integrating the host genome or enter an episomal form.

Figure 3.

Viral escape from T cells and NK cells. Viruses generate mutants of their sequence thereby either preventing peptide binding to MHC molecule (1) or by creating a variant unable to trigger a new cellular response (original antigenic sin, (2)). The recognition of virus by T cells is blocked by the downregulation of MHC molecules (Figure 1), whereas this would activate NK cells. To avoid this, viruses express MHC class I homologues (3) which bind to NK inhibitory receptors, and they allow the presentation of HLA‐C and E molecules (4) which are also recognised by these NK cell receptors. A further evasion strategy involves virus inhibiting the expression of NK activating receptor ligands such as MICA, MICB or UL16‐binding protein (ULBP) (5).



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Further Reading

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Urbani S, Amadei B, Tola D et al. (2006) PD‐1 expression in acute hepatitis C virus (HCV) infection is associated with HCV‐specific CD8 exhaustion. Journal of Virology 80(22): 11398–11403.

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Simmons, Ruth A, Willberg, Christian B, and Paul, Klenerman(Jun 2013) Immune Evasion by Viruses. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0024790]