Month: February 2023

A group from Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, France, etc. has reported about structural and functional analysis of BK polyomavirus mutants regarding the infectivity.
https://pubmed.ncbi.nlm.nih.gov/36790933/

BK polyomavirus (BKPyV) is a small, non-enveloped, double-stranded DNA virus with an icosahedral capsid formed by 72 capsomers, where a capsomer is an association of a pentamer of the VP1 protein. BKPyV is known to interact with the urothelium and kidney epithelium through the gangliosides GT1b and GD1b, but also via other b-series gangliosides characterized by their α2-8-linked-disialyl moieties attached to the first galactose from the reducing end. BKPyV is an opportunistic virus with a prevalence of 80% in the worldwide population. Usually, infections occur asymptomatically during childhood and then lead to latency or persistence in the kidneys.

In this study, four variant forms of the VP1 protein were discussed. These variants had accumulated multiple mutations in the BC loop region of the VP1 protein, which is involved in the direct interaction of the virus with sialic acids. Those variants contained double mutant K69N E82Q (N-Q), E73Q mutant, E73A mutant, and triple mutant A72V E73Q E82Q (VQQ). Cell lines 293TT and RS were used to test the infectivity of all variant pseudoviruses as well as wild-type (WT) subtype Ib2 pseudovirus. Both cell lines were shown to contain monosialylated GM2 and GM3 a-series gangliosides along with neutral globosides from the structural studies using MS. In addition, RS cells specifically expressed b-series disialylated gangliosides GD2 and GD3 carrying α2-8-linked-disialyl epitopes.

The followings were found.
The N-Q variant lost all ganglioside-binding activity but retained infectivity in 293TT cells through a sialic acid-independent pathway, whereas VQQ showed enhanced ganglioside binding but almost completely lost infectivity in 293TT cells. One plausible explanation of these observations is that the VQQ variant may have lost the ability to interact with the unknown entry receptor employed by the N-Q variant to infect 293TT cells, and that this interaction is required, in addition to sialic acid binding, for infectious entry.

A group from Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University, Okayama, Japan, etc. has reported that FUT8 is upregulated under oxidative stress.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0281516

The antioxidant response as defined by the Gene Ontology category includes 441 human genes, such as HMOX1 (Heme oxygenase 1) and GCLC (Glutamate—cysteine ligase catalytic subunit), which are typical antioxidant response genes. The expression of these genes helps reduce the oxidative condition in cells to protect them from oxidative stress. To test whether there is any changes in glycan expressions due to antioxidant responses, gene expressions in human keratinocyte cell line HaCaT were investigated with or without 5-hydroxy-4-phenyl-butenolide (5H4PB) and sulforaphane (SFN), which has been known to be an antioxidant.

It was found that FUT8 is upregulated in both cases (5H4PB and SFN) from gene analysis. This was also confirmed by flow cytometry using fluorescein-conjugated fucose binding lectin, UEA-I.

A group from Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan, etc. has reported that focoidans mediate decolonization of Pseudomonas aeruginosa from gut by inhibiting secreted virulence factor interactions with mucins and enriching Bacteroides population.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9896862/

Pseudomonas aeruginosa intestinal carriage rates are significantly higher in immunosuppressed individuals and hospitalized patients who therefore have increased risk of infections and antibiotic-associated diarrhea. Although gut microbiota acts as a barrier against intestinal pathogens, P. aeruginosa overcomes the resistance to colonization mediated by gut microbiota and innate immune system, by producing an impressive array of virulence factors. P. aeruginosa carries large protein systems that belong to two-partner secretion (TPS) family, and there is a conserved hemagglutinin (HA) domain in this TPS. The TPS system effectors are designated as major virulence determinants that are beneficial to Gram-negative pathogens (Pseudomonas is a Gram-negative).

Nutritional grade fucoidans 0.5% (w/v), from Fucus vesiculosus (FV) and Ascophyllum nodusum (AN), were supplemented in the drinking water of mice for 19 days. Among the mice that were fed with fucoidans for 14 days p.i., two patterns of decolonization were observed: (1) P. aeruginosa was eliminated from a higher proportion of the mice with time, (2) but in the remaining mice P. aeruginosa persisted throughout the study period but with declining bacterial loads over time. Of note, between p.i. day 15 and day 30 among the fucoidan fed groups proportion of the mice that were decolonized further increased to 60% (P < 0.05). It was found that there are two mechanisms by which fucoidans mediate their protective effects: first, inhibition of virulence factors TPS interactions with mucins and second, selectively promoting the growth of beneficial Bacteroides species. IC50s of interaction between TPS and intestinal mucins by FV fucoidan and AN fucoidan were less than 1 μg/mL.

A group from Research Team for Geriatric Medicine (Vascular Medicine), Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan. etc. has reported about spatiotemporal changes of tissue glycans depending on localization in cardiac aging.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9841240/

To investigate the characteristics of glycans in mouse cardiac tissues, eight parts of the short-axis slices from normal female mouse hearts, including the left ventricular wall (ventral sides and dorsal sides), the papillary muscle, and the ventricular septum were analyzed for three age groups (2 months, 12–14 months, and 23–25 months) using the lectin microarray.

The glycan profiles of the eight areas of the hearts of 2-month-old mice were analyzed in detail using PCA. Interestingly, it was fond that glycan profiles differ in each region of the cardiac tissue. For instance, papillary muscle and ventricular septum were characterized by sialic acid residues, and ventral left ventricular wall were characterized by O-glycan residues and large-branched and asialo N-glycan residues.

It was also found that sialic acid resides decreases with aging, although the rate of change varied from area to area.