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How A Latent Virus Eludes Immune Defenses

For a virus to survive, it must elude the ever vigilant immune sentinels of its host. A latent virus can escape immune detection if it resides in nondividing cells and doesn’t produce any proteins. No viral proteins means no red flags for immune cells. If the virus targets one of the many cell types that rarely divide, it’s relatively safe while latent. But some viruses, like the gamma-herpesvirus, infect B cells of the immune system, which occasionally divide. The gamma-herpesvirus genome persists as circular pieces of DNA called episomes. When an infected B cell divides, the latent gamma-herpes virus episome must replicate and segregate into daughter cells along with the cell’s genome. Viral replication and segregation requires the services of a protein called the episome maintenance protein—a potentially recognizable target for immune cells.

Gamma-herpesviruses, including Epstein-Barr virus (EBV) and Kaposi’s sarcoma–associated herpesvirus (KSHV), can induce uncontrolled lymphocyte (immune cell) proliferation and result in lymphoma, Hodgkin’s disease, and Kaposi’s sarcoma. These diseases arise from the persistent latent infections that take hold after initial infections are controlled by immune defenses. The episome maintenance protein produced by EBV, called EBNA-1, harbors an amino acid element in its epitope—the region that binds to a T cell and triggers an immune response—that helps the viral protein evade the killer T cells that could destroy it. Lab studies show that the amino acid element limits EBNA-1’s interaction with T cells by inhibiting synthesis and, to a lesser degree, degradation of the protein. How this evasive action works or helps the virus in a living organism is not entirely clear. But if T cells aren’t presented with bits of viral protein, they have no way of knowing the virus is present.

In a new study, Neil Bennett, Janet May, and Philip Stevenson explore this question by studying virus–host interactions in mice infected wit
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Source:PLoS Biology


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