Sialylation and fucosylation modulate inflammasome-activating eIF2 Signaling and microbial translocation during HIV infection

Mucosal Immunol. 2020 Sep;13(5):753-766. doi: 10.1038/s41385-020-0279-5. Epub 2020 Mar 9.


An emerging paradigm suggests that gut glycosylation is a key force in maintaining the homeostatic relationship between the gut and its microbiota. Nevertheless, it is unclear how gut glycosylation contributes to the HIV-associated microbial translocation and inflammation that persist despite viral suppression and contribute to the development of several comorbidities. We examined terminal ileum, right colon, and sigmoid colon biopsies from HIV-infected virally-suppressed individuals and found that gut glycomic patterns are associated with distinct microbial compositions and differential levels of chronic inflammation and HIV persistence. In particular, high levels of the pro-inflammatory hypo-sialylated T-antigen glycans and low levels of the anti-inflammatory fucosylated glycans were associated with higher abundance of glycan-degrading microbial species (in particular, Bacteroides vulgatus), a less diverse microbiome, higher levels of inflammation, and higher levels of ileum-associated HIV DNA. These findings are linked to the activation of the inflammasome-mediating eIF2 signaling pathway. Our study thus provides the first proof-of-concept evidence that a previously unappreciated factor, gut glycosylation, is a force that may impact the vicious cycle between HIV infection, microbial translocation, and chronic inflammation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiretroviral Therapy, Highly Active
  • Biodiversity
  • Colon, Sigmoid / immunology
  • Colon, Sigmoid / metabolism
  • Colon, Sigmoid / microbiology
  • Dysbiosis
  • Epitopes, T-Lymphocyte / immunology
  • Eukaryotic Initiation Factor-2 / metabolism*
  • Gastrointestinal Microbiome* / immunology
  • Glycosylation
  • HIV Infections / drug therapy
  • HIV Infections / immunology
  • HIV Infections / metabolism*
  • HIV Infections / virology
  • Humans
  • Immunocompromised Host
  • Inflammasomes / metabolism*
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / pathology
  • Metagenome
  • Metagenomics / methods
  • Protein Processing, Post-Translational
  • Signal Transduction*
  • Viral Load


  • Epitopes, T-Lymphocyte
  • Eukaryotic Initiation Factor-2
  • Inflammasomes