Herpes Simplex Virus Glycoprotein I (HSV-gI)

Several reports have shown that Herpes simplex virus type 1 (HSV-1) seropositive individuals contain elevated numbers of TCR-γ/δ cells in their peripheral blood that are specific for infected cells. Researchers have shown that Herpes Simplex Virus Glycoprotein I (HSV-gI) may be involved in this process.

Introduction of HSV-gI

HSV-1 is a neurotrophic virus that infects mucosal or abraded skin surfaces of nonimmune individuals. The virus replicates and destroys cells at the portal of entry. In addition, the virus infects nerve endings and is transported by neuroaxonal flow to the nucleus of autonomic nervous system neurons in which a latent infection is established. Immunocompromised individuals develop viral encephalitis due to an inability to limit the spread of the virus. Numerous studies have demonstrated that both cellular and humoral arms of the immune system contribute to the recovery from infection; however, T cells are ultimately required to protect the host. Spread of HSV by both the extracellular and cell-to-cell routes requires viral membrane glycoproteins gB, gD, and gH-gL. Mutant HSVs with deletions affecting gB, gD, gH, or gL cannot enter cells, and if the mutants are grown on complementing cells (to provide the missing glycoprotein), the viruses can enter cells but do not subsequently spread beyond the initially infected cell. Glycoproteins gE and gI, which form a functional complex (gE-gI), play an important role in cell-to-cell spread but do not affect the production of infectious virus or the rate at which extracellular virus particles bind to or enter cells, whether the virus is applied to the apical or basolateral surfaces of the cells.

Fig.1 HSV glycoproteins. (Goins, 2016)

Researches of HSV-gI and γδ T Cells

T cell receptor γδ cells prove to be a critical immunoregulatory population in both bacterial and viral pathogenesis, including herpes simplex virus (HSV)-1 infections. An abundance of recent evidence suggests that TCRγδ cells recognize unprocessed Ags directly. For instance, as documented for HSV-1 glycoprotein I-reactive cells as well as two MHC alloreactive TCRγδ cell clones, none of the known factors involved in MHC class I or II Ag processing affect TCRγδ Ag recognition. A recent report has described that the HSV-1 glycoprotein I (gI)-specific TCRγδ cell clone TgI4.4 (a murine TCRγδ cell clone) directly recognizes gI, independent of classical Ag processing or presentation. The research shows that gI recognition by TgI4.4 is conformationally dependent. Moreover, TgI4.4 recognizes the gI protein directly since completely deglycosylated forms of gI are efficiently recognized. The ability of TgI4.4 to recognize a nonglycosylated form of gI suggests that HSV-1 recognition by TCRγδ cells in vivo is not limited by cell-specific glycosylation patterns or glycosylation-dependent conformational influences.

TCR-γ/δ cells can respond to and suppress HSV-1 infection. However, the mechanism of the protective response, such as the nature of the antigenic ligands and the effector functions used by the protective TCR-γ/δ cell population, remains to be elucidated. How important a role HSV-gI plays in this process also needs more evidence.

Reference

1. Goins, W. F.; et al. Retargeting of herpes simplex virus (HSV) vectors. Curr Opin Virol.2016, 21: 93-101.