Phase-dependent immune evasion of herpesviruses.
نویسندگان
چکیده
Viruses employ various modes to evade immune detection. Two possible evasion modes are a reduction of the number of epitopes presented and the mimicry of host epitopes. The immune evasion efforts are not uniform among viral proteins. The number of epitopes in a given viral protein and the similarity of the epitopes to host peptides can be used as a measure of the viral attempts to hide this protein. Using bioinformatics tools, we here present a genomic analysis of the attempts of four human herpesviruses (herpes simplex virus type 1-human herpesvirus 1, Epstein-Barr virus-human herpesvirus 4, human cytomegalovirus-human herpesvirus 5, and Kaposi's sarcoma-associated herpesvirus-human herpesvirus 8) and one murine herpesvirus (murine herpesvirus 68) to escape from immune detection. We determined the full repertoire of CD8 T-lymphocyte epitopes presented by each viral protein and show that herpesvirus proteins present many fewer epitopes than expected. Furthermore, the epitopes that are presented are more similar to host epitopes than are random viral epitopes, minimizing the immune response. We defined a score for the size of the immune repertoire (the SIR score) based on the number of epitopes in a protein. The numbers of epitopes in proteins expressed in the latent and early phases of infection were significantly smaller than those in proteins expressed in the lytic phase in all tested viruses. The latent and immediate-early epitopes were also more similar to host epitopes than were lytic epitopes. A clear trend emerged from the analysis. In general, herpesviruses demonstrated an effort to evade immune detection. However, within a given herpesvirus, proteins expressed in phases critical to the fate of infection (e.g., early lytic and latent) evaded immune detection more than all others. The application of the SIR score to specific proteins allows us to quantify the importance of immune evasion and to detect optimal targets for immunotherapy and vaccine development.
منابع مشابه
Interferon, the Cell Cycle and Herpesvirus
Herpesviruses are a large group of successful, and widely distributed, double-stranded DNA viruses of serious medical and veterinary importance. Although they infect many different animal species, they are host specific at the individual species level. On the other hand, they share a common life style, first with an acute infection in epithelial cells which is followed by the establishment of p...
متن کاملThe Epstein-Barr Virus Glycoprotein gp150 Forms an Immune-Evasive Glycan Shield at the Surface of Infected Cells
Cell-mediated immunity plays a key role in host control of viral infection. This is exemplified by life-threatening reactivations of e.g. herpesviruses in individuals with impaired T-cell and/or iNKT cell responses. To allow lifelong persistence and virus production in the face of primed immunity, herpesviruses exploit immune evasion strategies. These include a reduction in viral antigen expres...
متن کاملHuman Herpesviridae Methods of Natural Killer Cell Evasion
Human herpesviruses cause diseases of considerable morbidity and mortality, ranging from encephalitis to hematologic malignancies. As evidence emerges about the role of innate immunity and natural killer (NK) cells in the control of herpesvirus infection, evidence of viral methods of innate immune evasion grows as well. These methods include interference with the ligands on infected cell surfac...
متن کاملViral Inhibition of the Transporter Associated with Antigen Processing (TAP): A Striking Example of Functional Convergent Evolution
Herpesviruses are large DNA viruses that are highly abundant within their host populations. Even in the presence of a healthy immune system, these viruses manage to cause lifelong infections. This persistence is partially mediated by the virus entering latency, a phase of infection characterized by limited viral protein expression. Moreover, herpesviruses have devoted a significant part of thei...
متن کاملA seek-and-hide game between Cd1-restricted T cells and herpesviruses.
T and NK cells collaborate to control viral infections, discerning minute differences between infected and uninfected cells. At the same time, viruses have evolved to escape this discovery. In this issue of the JCI, Ganem and colleagues show that Kaposi sarcoma-associated herpesvirus (KSHV) inhibits CD1d presentation to T cells. This novel immune evasion strategy highlights the importance of CD...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Journal of virology
دوره 81 17 شماره
صفحات -
تاریخ انتشار 2007