Virion glycosylation influences mycobacteriophage immune recognition

Freeman, Krista G.; Robotham, Anna C.; Parks, Olivia B.; Abad, Lawrence; Jacobs-Sera, Deborah; Lauer, Michael J.; Podgorski, Jennifer M.; Zhang, Yu; Williams, John V.; White, Simon J.; Kelly, John F.; Hatfull, Graham F.; Pope, Welkin H.

doi:10.1016/j.chom.2023.05.028

Virion glycosylation influences mycobacteriophage immune recognition

Journal Article · Fri Jun 16 00:00:00 EDT 2023 · Cell Host & Microbe

DOI:https://doi.org/10.1016/j.chom.2023.05.028· OSTI ID:2424203

Freeman, Krista G. ^[1]; Robotham, Anna C. ^[2]; Parks, Olivia B. ^[3]; Abad, Lawrence ^[1]; Jacobs-Sera, Deborah ^[1]; Lauer, Michael J. ^[1]; Podgorski, Jennifer M. ^[4]; Zhang, Yu ^[5]; Williams, John V. ^[5]; White, Simon J. ^[4]; Kelly, John F. ^[2]; Hatfull, Graham F. ^[1]; Pope, Welkin H. ^[6]

Univ. of Pittsburgh, PA (United States)
National Research Council of Canada, Ottawa, ON (Canada). Human Health Therapeutics
UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA (United States)
Univ. of Connecticut, Storrs, CT (United States)
UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA (United States); University of Pittsburgh School of Medicine, Pittsburgh, PA (United States)
Chatham University, Pittsburgh, PA (United States)

Glycosylation of eukaryotic virus particles is common and influences their uptake, trafficking, and immune recognition. In contrast, glycosylation of bacteriophage particles has not been reported; phage virions typically do not enter the cytoplasm upon infection, and they do not generally inhabit eukaryotic systems. We show here that several genomically distinct phages of Mycobacteria are modified with glycans attached to the C terminus of capsid and tail tube protein subunits. These O-linked glycans influence antibody production and recognition, shielding viral particles from antibody binding and reducing production of neutralizing antibodies. Glycosylation is mediated by phage-encoded glycosyltransferases, and genomic analysis suggests that they are relatively common among mycobacteriophages. Putative glycosyltransferases are also encoded by some Gordonia and Streptomyces phages, but there is little evidence of glycosylation among the broader phage population. The immune response to glycosylated phage virions in mice suggests that glycosylation may be an advantageous property for phage therapy of Mycobacterium infections.

View Accepted Manuscript (DOE)

Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Environmental Molecular Sciences Laboratory (EMSL)

Sponsoring Organization:: Howard Hughes Medical Institute; National Institutes of Health (NIH); USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 2424203

Journal Information:: Cell Host & Microbe, Journal Name: Cell Host & Microbe Journal Issue: 7 Vol. 31; ISSN 1931-3128

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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