Herpes simplex virus type 2 tegument protein UL46 (UL46)

Herpes simplex virus type 2 tegument protein UL46, also known as VP11/12, is a major structural component of the HSV-2 virion that resides in the tegument layer between the capsid and the envelope [1, 11]. It plays a dual role in the viral life cycle: it acts as a modulator of the viral transactivator VP16 (UL48) to promote the expression of immediate-early genes during the initiation of lytic infection, and it serves as a potent immune evasion factor [2, 5, 12]. UL46 suppresses the host's innate immune response by inhibiting the STING-mediated interferon signaling pathway, specifically by targeting TBK1 and preventing its activation [2, 7]. In the context of disease, UL46 is central to the pathogenesis of genital herpes and has been identified as a key target for therapeutic vaccines [9, 13]. Experimental candidates such as HerpV and Vaxfectin-formulated DNA vaccines utilize UL46-derived antigens to elicit robust CD4+ and CD8+ T-cell responses, which are intended to reduce viral shedding and the frequency of clinical lesions [11, 13, 16]. However, a significant therapeutic challenge involves the potential for increased HIV-1 acquisition risk, as the induction of activated CD4+ T cells in the genital mucosa may provide more targets for HIV entry [13, 18].

Other names

VP11/12Virion protein 11/12Phosphoprotein UL46

Therapeutic vaccination to induce T-cell mediated immunity against viral antigens