Virus-induced appearance of the selectin ligand sLeX in herpes simplex virus type 1-infected T-cells: Involvement of host and viral factors

Abstract

Circulating leukocytes that express selectin ligands such as the carbohydrate epitope sialyl Lewis X (sLeX) may interact with endothelial selectins, resulting in transmigration of the leukocyte across the endothelial wall to adjacent tissue. Due to the potential of selectin-ligand interactions as targets in viral pathogenesis, we aimed at determining whether herpes simplex virus type 1 (HSV1) is able to induce the appearance of sLeX at the surface of infected leukocytes. We found that HSV1 infection of a T-cell line resulted in transcriptional activation of human fucosyltransferase genes FUT3, FUT6 and FUT7, the two latter genes encoding the fucosyltransferases rate limiting for sLeX synthesis. Flow cytometry and confocal microscopy demonstrated that HSV1 infection resulted in a 2-fold rise in the proportion of sLeX-positive cells. Increased levels of FUT3, FUT6 and FUT7 RNA were detected already at 3 h post infection, and treatment with cycloheximide, a translation inhibitor, blocked a HSV1-induced increase in the expression of FUT3, FUT6 and FUT7 RNA, suggesting involvement of viral or cellular proteins. Studies with infectious viral mutants indicated that the viral immediate early (α) protein ICP0 is essential for the initiation of FUT7 though not for FUT3 or FUT6 transcription. In CD3+ cells, derived from peripheral blood mononuclear cells, HSV1 infection induced expression of FUT3, FUT5 and FUT6, whereas FUT7 was not altered. The mean sLeX fluorescence intensity of CD3+ cells was significantly higher in HSV1-infected CD3+ cells. This suggests that infected leukocytes during HSV1 viremia may express selectin ligands with possible but as yet unproven roles in viral pathogenesis.

Sensing of cell-associated HTLV by plasmacytoid dendritic cells is regulated by dense β-galactoside glycosylation

“…By analogy to previously reported abilities of several viruses to modify ECM composition of the host cells to favor their own dissemination and/or immune escape [62–64], one might speculate that the chronic infection by HTLV modulates the cell surface glycan pattern [65]. We showed that terminal β-galactoside glycosylation density is inversely correlated with the ability of infected cells to promote contact-dependent pDC IFN-I production.…”

Apoptosis, Autophagy, and Pyroptosis: Immune Escape Strategies for Persistent Infection and Pathogenesis of Classical Swine Fever Virus

“…The virus-induced apoptosis of host cells is one of the important mechanisms of viral pathogenesis [22]. Apoptosis is the first line of defense against viral infection in host cells [16]. The host cells quickly start the apoptotic process under the stimulation of viruses and restrict the replication and transmission of viruses by quickly clearing the infected cells [16,22,36].…”

“…Apoptosis is the first line of defense against viral infection in host cells [16]. The host cells quickly start the apoptotic process under the stimulation of viruses and restrict the replication and transmission of viruses by quickly clearing the infected cells [16,22,36]. During virus infection, apoptosis can be triggered by diverse cellular signals, including the death receptor-mediated extrinsic pathway, the intrinsic mitochondrial pathway, the granzyme B-mediated pathway, and the endoplasmic reticulum stress-mediated pathway.…”

“…The occurrence, development, and outcome of infectious diseases are the result of interaction between pathogens and hosts. In the long-term struggle between host and virus, the host initiates different forms of cellular biological processes to restrict viral replication [16][17][18]. However, in order to achieve persistent infection, viruses have evolved a variety of mechanisms to regulate cellular biological processes, thereby affecting the host inflammatory response and even cell survival, thus avoiding the host antiviral immune response [19][20][21][22].…”

High expression of FUT3 is linked to poor prognosis in clear cell renal cell carcinoma

“…A recent study illustrated the proliferation and other malignant properties such as migration and invasion capability of gastric carcinoma cell line can be inhibited by FUT3 gene silencing [ 21 ]. In contrast, we cannot confirm that the sLe x is all synthesized by FUT3, since FUT4, FUT5, FUT6, FUT-9 and FUT7 also have the α(1,3)-fucosyltransferase activity and their function in Lewis antigen synthesis of different tissue has as well been proved [ 22 – 24 ].…”