RESUMO
The disruption of antiviral sensors and the evasion of immune defences by various tactics are hallmarks of EBV infection. One of the EBV latent gene products, LMP1, was shown to induce the activation of signalling pathways, such as NF-κB, MAPK (JNK, ERK1/2, p38), JAK/STAT and PI3K/Akt, via three subdomains of its C-terminal domain, regulating the expression of several cytokines responsible for modulation of the immune response and therefore promoting viral persistence. The aim of this review is to summarise the current knowledge on the EBV-mediated induction of immunomodulatory molecules by the activation of signal transduction pathways with a particular focus on LMP1-mediated mechanisms. A more detailed understanding of the cytokine biology molecular landscape in EBV infections could contribute to the more complete understanding of diseases associated with this virus.
Assuntos
Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Transdução de Sinais , Proteínas da Matriz Viral , Humanos , Proteínas da Matriz Viral/metabolismo , Proteínas da Matriz Viral/imunologia , Proteínas da Matriz Viral/genética , Herpesvirus Humano 4/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/virologia , Infecções por Vírus Epstein-Barr/metabolismo , Citocinas/metabolismo , Citocinas/imunologia , Animais , Imunomodulação , Interações Hospedeiro-Patógeno/imunologia , NF-kappa B/metabolismo , Latência Viral/imunologiaRESUMO
The molecular diversity of Epstein-Barr virus (EBV) is exceptionally complex and based on the characterization of sequences coding for several viral genes. The aim of this study was to analyze the distribution of EBV types 1 and 2 and to characterize LMP1 variants in a cohort of 73 patients with infectious mononucleosis (IM), as well as to investigate a possible association between viral diversity and relevant clinical parameters. Population-based sequencing of EBNA-2 gene showed the presence of EBV type 1 in all IM patients. Analysis of LMP1 gene found a restricted repertoire of LMP1 variants with the predominance of wild-type B95-8, China1, Mediterranean and North Carolina variants with the presence of more than one LMP1 variant in 16.4% of patients. Co-infections with different LMP1 variants were associated with significantly higher levels of C-reactive protein and lower levels of maximal neutrophil counts and minimal platelet count. The results of this study have shown a narrow repertoire of LMP1 variants and an exclusive presence of EBV type 1 in a cohort of IM from Croatia, suggesting a characteristic local molecular pattern of this virus. The clinical importance of distinct immunobiological features of IM patients with LMP1 variant co-infections needs to be investigated further.
