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Latent Membrane Protein LMP2A Impairs Recognition of EBV-Infected Cells by CD8+ T Cells


Epstein-Barr virus (EBV) is carried by most humans. It can cause several types of cancer. In healthy infected people, EBV persists for life in a "latent" state in white blood cells called B cells. For infected persons to remain healthy, it is crucial that they harbor CD8-positive "killer" T cells that recognize and destroy precancerous EBV-infected cells. However, this protection is imperfect, because the virus is not eliminated from the body, and the danger of EBV-associated cancer remains. How does the virus counteract CD8+ T cell control? Here we study the effects of latent membrane protein 2A (LMP2A), which is an important viral molecule because it is present in several types of EBV-associated cancers, and in latently infected cells in healthy people. We show that LMP2A counteracts the recognition of EBV-infected B cells by antiviral killer cells. We found a number of mechanisms that are relevant to this effect. Notably, LMP2A disturbs expression of molecules on B cells that interact with NKG2D, a molecule on the surface of CD8+ T cells that aids their activation. In this way, LMP2A weakens important immune responses against EBV. Similar mechanisms may operate in different types of LMP2A-expressing cancers caused by EBV.


Vyšlo v časopise: Latent Membrane Protein LMP2A Impairs Recognition of EBV-Infected Cells by CD8+ T Cells. PLoS Pathog 11(6): e32767. doi:10.1371/journal.ppat.1004906
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004906

Souhrn

Epstein-Barr virus (EBV) is carried by most humans. It can cause several types of cancer. In healthy infected people, EBV persists for life in a "latent" state in white blood cells called B cells. For infected persons to remain healthy, it is crucial that they harbor CD8-positive "killer" T cells that recognize and destroy precancerous EBV-infected cells. However, this protection is imperfect, because the virus is not eliminated from the body, and the danger of EBV-associated cancer remains. How does the virus counteract CD8+ T cell control? Here we study the effects of latent membrane protein 2A (LMP2A), which is an important viral molecule because it is present in several types of EBV-associated cancers, and in latently infected cells in healthy people. We show that LMP2A counteracts the recognition of EBV-infected B cells by antiviral killer cells. We found a number of mechanisms that are relevant to this effect. Notably, LMP2A disturbs expression of molecules on B cells that interact with NKG2D, a molecule on the surface of CD8+ T cells that aids their activation. In this way, LMP2A weakens important immune responses against EBV. Similar mechanisms may operate in different types of LMP2A-expressing cancers caused by EBV.


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