Study on the Carbohydrate Interactions Between Chloroviruses and Immune System
The team of Cristina De Castro from the University of Napoli and Fabrizio Chiodo from the Vrije University Amsterdam published an article titled "Carbohydrate-mediated interactions between chloroviruses and the immune system" in Communications Biology. The article studied the Carbohydrate-mediated interactions between chloroviruses and the Immune System from different angles.
Studies have shown that some large viruses are part of the human virome. Among these viruses, chlorovirus is a common inland water virus. According to statistics, humans will encounter chloroviruses many times in their lifetime. Based on this, the authors hypothesized that chloroviruses and humans may interact at the molecular and immune levels. Therefore, this article focuses on the interaction between chlorovirus surface carbohydrate molecules and human monocyte-derived dendritic cells (moDC) and mouse macrophages.
Chlorella viruses are divided into four categories according to their host algae. The length of their major capsid protein (MCP) carbohydrate chains ranges from 4 to 10 residues, but all have a conserved core region consisting of 4 residues.
In order to study the effects of the carbohydrate structures encoded by these viruses on the host immune system, the authors selected representatives of three types of chlorophyll viruses: PBCV-1, ATCV-1, and Osy-NE-5. The first two are related to the human virus group, and the latter is similar to ATCV-1 in structure (only the rhamnose configuration is different).
The article also selected three antigenic variants of PBCV-1 (P91, PIL6, and EIL-1) to analyze the role of viral carbohydrates in innate immune recognition.
Fig. 1 The N-glycan structures of the chlorovirus glycoproteins used in this study. (Speciale, et al., 2024)
Evaluate the interaction of viral MCPs with a panel of Human/Plant Lectins – as these proteins play an important role in the host immune system.
In the non-antigenic variants, PBCV-1 binds strongly to DC-SIGN, and OSy-NE-5 binds strongly to Langerin. In the antigenic variants, P91 binds more strongly to MGL, EIL-1 binds more strongly to DC-SIGN and Langerin, and P1L1 interacts less well with all three lectins. These differences are mainly related to whether the Glycoprotein has a terminal D-Rha residue - although PBCV-1 and P91 also have an exposed D-Man residue (whose structure is similar to the D-Rha residue and can also be recognized by lectins), they may be affected by steric hindrance of other sugar residues and cannot be recognized by DC-SIGN and Langerin.
The article also further tested the binding of viral MCPs to four plant lectins - the selected lectins can recognize Gal and (or) GalNAc residues. The results showed that all MCPs were recognized by the four lectins to varying degrees - among which RCA had the strongest binding to viral MCPs, while HPA had a clear preference for PBCV-1 and PIL6.
The induction effects of viral MCPs on the cytokines IL-6 and IL-10 were monitored in moDCs and the mouse macrophage cell line RAW264.7.
Antigen-presenting cells produce IL-6, an inflammatory cytokine, and IL-10, an anti-inflammatory cytokine, after exposure to viral and other pathogen-associated molecular patterns. The authors first examined the effects of six chlorovirus MCPs on moDCs. Among the non-antigenic variants, PBCV-1 did not induce the production of IL-6 or IL-10; ATCV-1 induced the production of IL-6, but not IL-10; Osy-NE-5 strongly upregulated the secretion of IL-6 and IL-10. Among the antigenic variants, P91 showed only a very weak induction effect, while the other two variants showed a strong induction effect.
The same experiment was performed in the mouse macrophage cell line RAW264.7, and the results were similar.
Sera from healthy donors were screened for IgG that recognize these Glycosylated MCPs to assess whether the virus activates the human adaptive immune system.
The authors examined sera from 12 healthy donors. Most donor sera contained IgG antibodies to ATCV-1; in contrast, almost all contained low or undetectable levels of IgG antibodies to PBCV-1. Surprisingly, all donor sera contained high levels of IgG antibodies to P1L6. These results confirm that humans have antibodies against some of the MCPs of chlorovirus and their variants—suggesting that some corresponding Glycan patterns exist in the human environment.
In summary, these diverse experimental results demonstrate that host innate and adaptive systems are able to recognize viral surface glycoproteins from large viruses and that these recognitions are associated with unique viral N-glycan structures, which are critical for the development of new therapeutics, diagnostics, and molecular adjuvants.
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