Archive 21/4/25

The common knowledge in HIV infection is that two types of receptors are related to the infection to CD4⁺ T cells. First of all, an envelop glycoprotein of HIV called gp120 binds to the first receptor CD4, then binds to the second receptor, CCR5 or CXCR4, and initiates membrane fusion between HIV and T cell. A group from University of Sydney, etc. has reported what major HIV target cells in human anogenital tissues in the HIV infection.
https://www.nature.com/articles/s41467-021-22375-x

Authors have identified two types of cells, one is D14⁺CD1c⁺ monocyte-derived dendritic cells（CD14⁺CD1c⁺MDDC, and the other is　Langerin-expressing dendritic cells 2（Langerin⁺ cDC2). Langerin is a C-type lectin which is selectively expressed on langerhans cells (LC), a subset of dendritic cells distributing in dermis and mucosa. The binding specificity of langerin is known to be high mannose and galactose with sulfated 6th site. Furthermore, it was found that HIV infection was correlated with Siglec-1 expression on CD14⁺ MDDC. In this way, these cells bind HIV and mediate efficient HIV uptake, and transfer to CD4⁺ T cells.

From a view point of glycan and lectin, it is so important to understand the relationship between C-type lectins on host cells and HIV gp120 glycoproteins.

A group from University of Liverpool has reported results of random forests model (one of machine learning methods) to predict the animal host of SARS-CoV-2.
https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009149

A figure below shows stacked bar plots of predicted probabilities of each host category for coronavirus RNA sequences, assuming bird, camelid, carnivore, human, rodent, swine, yangochiroptera, and yinpterochiroptera as potential hosts. It is clearly shown that MARS-CoV has camelid host, SARS-CoV has carnivore host, and SARS-CoV2 seems to have a bat host (suborder Yinpterochiroptera). While the random forests model supports bats as the ultimate origin of SARS-CoV-2, the involvement of intermediate hosts remains unclear.

A group from Rowan University, Stratford, USA, etc. has suggested that Maackia amurensis lectin (MAL, MAA, MASL as abbreviated names) could be effctive in inhibiting SARS-CoV-2 infection.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019238/

Oral squamous cells were used as a model cell in this study. Transcriptome analysis was done to investigate effects of MAL onto ACE2, ADAM17, Furin, and Glycosyltransferases (GalNAc-T, ST6GalNAc-1, and ST6GalNAc-2）.
Interestingly, it was shown that those decreased in a MAL dose dependent manner. For instance, at a dose of 1925nM of MAL, ACE2 mRNA level decreased by 60％, ADAM17 by 40％, and ST6GalNAc-1 by 60%. As a result of these events, MAL decreases inflammatory signaling events that would otherwise lead to activation of the IL6 amplifier implicated in COVID-19 induced ARDS

MAL is known to have binding specificity to α2-3Sia.

A group from San Martino Policlinico Hospital, Genoa, Italy, etc. has reported on characteristics of bronchoalveolar lavage fluid (BALF) collected from COVID-19 patients.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049078/

BALF cellularity was mainly composed of neutrophils and macrophages (neutrophils were more abundant than macrophages). The median value of macrophage percentages was higher in non-survivors compared to survivors (35% vs 20%). However, we must be cautious that all the differences shown in a table below are not statistically significant.

A group from Northwest University, Xi’an, China, etc. has reported a potential glycan biomarker for Esophageal squamous cell carcinoma (ESCC)
.
https://www.frontiersin.org/articles/10.3389/fchem.2021.637730/full

Saliva was used as a sample in this study, and saliva was centrifuged to remove insoluble components and a protease inhibitor was added. Lectin microarrays using 37 lectins were used for investigating differences in glycosylation patterns between healthy volunteers (HV) and ESCC patients. As a result, it was found that DSA and ECA lectins are specific to ESCC, and Galβ1-4GlcNAc-containing N-glycans could be potential biomarkers for ESCC.

A group from University Göttingen, etc. has alarmed a possibility in reinfection of mutated SARS-CoV-2 in farmed mink to human.
https://pubmed.ncbi.nlm.nih.gov/33857422/

Transmission of SARS-CoV-2 from humans to farmed mink has been observed in Europe and USA. Substitution D614G, which is dominant in SARS-CoV-2 from humans, was also found in viruses from mink, and a mink-specific mutation Y453F (mutant D614G+Y453F) or Y453F in conjunction with H69Δ, H70Δ (mutant D614G+H69Δ/H70Δ/Y453F) were also found in mink. The Y453F mutation locates in RBD, and reduced inhibition by human serum samples tested. The neutralizing titer IC₅₀ increased by 1.62 times with this mutation, and the neutralizing titer of REGN10933, which is one component of a cocktail therapy (REGN-COV2), also increased with this mutation.

New emerging variants generated through transmission from humans to wild animals could represent a future threat to human health.

A group from Vector State Research Center of Virology and Biotechnology, etc. has investigated binding specificity of SARS-CoV-2 Spike protein to a various glycans with using ELISA assays.
SARS-CoV-2 Spike protein does not bind to sialic acid, unlike the case of influenza virus, but has affinity to a lactosamine family (Galβ1-3GlcNAc, Galβ1-4GlcNAc, etc.).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905424/