# Immunological Aspects of EBV and Oral Mucosa Interactions in Oral Lichen Planus
## 5 Role of Langerhans Cells in Oral Lichen Planus Pathogenesis
In a series of studies by [PERSON] et al., it was shown that interaction between EBV BMRF-2 and integrins is decisive for EBV infection in oral epithelial cells [94]. BMRF-2 is a ligand for \(\beta\)1, \(\alpha\)5, \(\alpha\)3, and \(\alpha\)v integrins and demonstrates the role of BMRF 2 in the lytic stage of infection, but the absence of BMRF-2 results in an approximately 50% reduction in EBV attachment to oral epithelial cells [99]. It is suggested that BMRF-2 may also play a crucial role in facilitating the spread of EBV progeny virions through the oral epithelial lateral membranes to other cells [100]. EBV has two life cycles, consisting of a latent cycle, a condition with persistent infection without productive viral replication, and a lytic cycle, a state in which new virions are produced [92]. EBV multiplies in oropharyngeal epithelial cells and establishes latency III, II, and I infections in B lymphocytes in primary infection, which is required for viral persistence, subsequent replication in epithelial cells, and the shedding of infectious virus in saliva. Latency II is possible only in epithelial cells, and latency II infection of oral epithelial cells and NK or T cells can lead to malignancies characterized by EBV genome presence and gene expression [101]. During EBV latent infection, three EBV-encoded latent proteins (LMP 1-3) and six EBV core antigens (EBNA 1-6) are expressed. B cell immortalization and cell cycle progression depend on EBNA-LP, EBNA2, and EBNA3C [88]. These latent proteins can also pathologically affect various molecular processes and pathways of the cell, thus playing a role in the pathogenesis of EBV-related cancers [102]. The process in the lytic cycle can be divided into three temporal and functional stages: immediate, early, and late [92]. Rta (encoded by BRLF1) and Zta (encoded by BZLF1) are viral transcription factors that mediate the transition from latent EBV infection to lytic viral replication. The viral transcription factors Rta (encoded by BRLF1) mediate the switching from latent EBV infection to lytic viral replication (encoded by BRLF1) and Zta (encoded by BZLF1). Rta is the main transactivator in epithelial cells, and Zta supports DNA replication and co-activates a subset of early promoters along with Rta. Both Rta and Zta are immediate early transcription factors that activate EBV-lytic gene expression. The products of the early genes are mainly involved in viral DNA replication, while the products of the late genes mainly support the formation of viral particles [103]. The lytic cycle of EBV is triggered when EBV-infected memory B cells differentiate into plasma cells, simultaneously stimulating productive EBV replication by releasing large amounts of EBV fragments that directly infect epithelial cells of the orophnx. The new virions further multiply and spread to other cells [104]. In oral saliva are found exosomes and microvesicles secreted by oral and tonsillar epithelial cells that promote intercellular communication. An examination of cultured oral epithelial cells reveals that the epithelium-specific miR-200 family of microRNAs releases a specific signal that initiates EBV lytic replication [105]. It should be noted that latent infection is recognized as the most important mode of infection in EBV-related cancers, and limited expression of a specific group of latent genes contributes to the disorder's development. In recent years, studies have shown that the EBV lytic phase may play a substantial role in EBV lytic gene expression, and its involvement in EBV tumorigenesis is often disclosed in tumor tissues and cell lines [106]. One of the EBV manifestations on the tongue, known as oral hairy leukoplakia, is clinically well diagnosed in immunosuppressed patients. In this case, EBV lytically infects normal differentiated oral epithelial cells of the _stratum spinosum_ and the _stratum granulosum_. The desquamating cells containing infectious virions shed into saliva [107; 108].