Archive 22/1/28

In SARS-CoV-2 unvaccinated cases, Omicron infection shows limited cross-reactive neutralization against other variants

A group from Gladstone Institutes, San Francisco, CA, USA, etc. has reported that infection with Omicron variant in unvaccinated individuals may not elicit effective cross-neutralizing antibodies against other variants. In vaccinated individuals, however, Omicron infection effectively induces immunity against itself and enhances protection against other variants.

To determine humoral immune responses induced by infection with the three different strains, sera from infected mice and tested their neutralization efficiency against SARS-CoV-2 strains were collected: WA1, Alpha, Beta, Delta, and Omicron. Efficient virus neutralization was defined by more than 50% reduction in plaque forming units at the lowest serum dilutions. Sera from Delta-infected mice showed the broadest cross-variant neutralization, effectively neutralizing all the strains except Beta. By contrast, while Omicron infection effectively neutralized Omicron itself, it exhibited limited (<50%) cross-neutralization of other strains. Sera from WA1-infected mice conferred effective protection against WA1, Alpha, and Delta, but not against Beta and Omicron. These results indicate limited immunity induced by Omicron relative to other strains, which may be due to its highly mutated spike protein or its lower replicative capacity. In human cases, interestingly, sera from vaccinated individuals with confirmed Omicron breakthrough infection showed the highest level of protection (>80%) against all strains, including Omicron as shown below.

Specific glycan structures observed in Cisplatin resistant Testicular Cancer

A group from Institute of Chemistry, Slovak Academy of Sciences, Bratislava, Slovakia, has reported about difference in glycan structures between cisplatin sensitive and resistant testicular cancer (TC) cell lines.

Testicular cancer is the most frequent type of cancer among young men aged between 15 and 34 years and represents 1.5% of all cancer types in men and 5% of urological tumours overall.
Cisplatin, as one of the very first metal-based chemotherapy drugs, is still widely used to treat patients with various types of cancers including TC. This drug is also effective in curing TC patients having metastases with cure rates of up to 90% and with a general survival rate of up to 95%. The reason why cisplatin works so effectively in treatment of GCTs is that such cells produce the embryonal stem cells. In turn, damaged embryonal stem cells need to be eliminated through apoptosis in order not to pass on mutations to the next generation. Loss of this embryonic feature might lie behind the development of cisplatin resistance.

Cisplatin binds to DNA and creates lesions (i.e. protein–DNA complexes and inter/intra-strand DNA adducts) which cannot be repaired by the DNA repair mechanisms, resulting in a disruption of synthesis of DNA, mRNA and proteins, promoting the accumulation of reactive oxygen species, activating signalling pathways and finally resulting in cell death.

Authors have found that DBA lectin could be the best probe for evaluating the resistance of TC lines, and also that HHL lectin could be used to prospect for cisplatin sensitive TC lines.

Correlation between lectin binding to human chorionic gonadotropin (hCG) of sensitive/resistant testicular cancer cell lines with cisplatin ID50

Metal oxide nano-particles could control soil-borne disease tomato bacterial wilt

A group from Key Laboratory of Biology of Crop Pathogens and Insects of Zhejiang Province, Institute of Biotechnology, Zhejiang University, Hangzhou 310058, China, etc. has reported on strategies for preventing and controlling soil-borne disease tomato bacterial wilt (TBW) with metal oxide Nano-particles (NPs).

Tomato bacterial wilt (TBW) is the most infectious soil-borne bacterial disease in the world. Ralstonia solanacearum is the causal agent of TBW and is recognized as a serious phytopathogen.

The application of CuONPs, FeONPs, and ZnONPs caused 24.3%, 54.6%, and 30.8% increases, respectively, in tomato plant length, compared to the corresponding diseased control. Similarly, TBW infected plants treated with three metal oxide NPs (CuO, FeO, and ZnO) resulted in 32.8%, 78.3%, and 30.6% increases in fresh weight, and 41.0%, 54.1%, and 40.0% increase in dry weight, respectively, compared to the control.

The application of the CuONPs, FeONPs, and ZnONPs treatments decreased the disease incidence significantly to 36.9%, 52.8%, and 42.8%, respectively, compared to the control plants.

From a study of rhizosphere biota, it was found that NPs could affect the abundance of bacteria in the rhizosphere soil to regulate the composition of the bacterial community. Therefore, it would be likely that changes in interaction between bacteria in the rhizosphere microbial community reduced the occurrence of TBW.

A method using glyco-antigen expressing nanoparticles (NPs) as vaccines

A group from Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA, etc. has reported on a method using glyco-antigen expressing nanoparticles (NPs) as vaccines.

Authors recently reported that glycosylated HIV-immunogen-bearing nanoparticles accumulate within follicles in a process mediated by mannose-binding lectin (MBL), which triggers complement deposition on the nanoparticle surface, transport to follicular dendritic cells (FDCs), and enhanced germinal center (GC) and serum antibody responses relative to non-accumulating nanoparticles.

Titrating the mean glycosylation of these particles from zero to 240 high-mannose glycans per NP resulted in steady increases in in vitro MBL binding as well as in vivo FDC localization. However, it starts to decrease with increasing the glycan density further (as shown below). These experiments provide an estimate of the minimal glycan patch density required to initiate MBL binding, which for the model ∼25 nm particles studied here was 2.1 × 10−3 mannose patches/nm2, corresponding to a mean separation of ∼21 nm between patches.
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SARS-CoV-2 omicron variant shows attenuated lung disease in mice and hamsters comparing to other variants

A group from the collaborative network of the SARS-CoV-2 Assessment of Viral Evolution (SAVE) program of the National Institute of Allergy and Infectious Diseases (NIAID) has reported that SARS-CoV-2 omicron variant shows attenuated lung disease in mice and hamsters, which parallels preliminary human clinical data.

Some recent studies (as also introduced in this blog) speculated that because mutations in the omicron spike protein overlap with ones known to promote adaptation to mouse hosts, the progenitor of omicron jumped from humans to mice, and then back into humans. In support of this, omicron but not Wuhan-1 RBD binds to murine ACE2. Hamsters also are highly susceptible to SARS-CoV-2 infection with similar pathological changes seen in lung tissues from COVID-19 patients. Using experimental data from multiple laboratories of the SAVE/NIAID consortium, authors report on the infectivity and pathogenesis of multiple omicron isolates in mice and hamsters.

Here is the data of comparison between omicron in BALB/c mice and beta variant. At 2 days-post-infection (dpi), infectious virus levels in the nasal turbinates and lungs were significantly lower (~1,000-fold, P < 0.001) in BALB/c mice infected with omicron compared to beta virus.

A comparison of infectious viral burden in hamster tissues at 3 dpi between delta and omicron viruses showed virtually no difference in nasal turbinates but substantially less infection of omicron in the lungs of hamsters.

Here is the comparison of lung pathology in Syrian hamsters after infection with delta or omicron viruses. Macroscopically, the lungs obtained from the delta-infected hamsters showed congestion and/or hemorrhage, but this was absent in omicron-infected animals. Overall, the Omicron variant replicates less efficiently in the lungs of Syrian hamsters, which results in less severe pneumonia compared to the delta variant.

Our experiments suggest that compared to other SARS-CoV-2 isolates (e.g., beta or delta), the Omicron variant infection is attenuated in laboratory mice and hamsters for causing infection and/or disease. While these results are consistent with the very preliminary clinical data in humans suggesting that omicron causes a more transmissible yet possibly milder respiratory infection, the basis for the attenuation in rodents remains unknown.

One pre-print study (also introduced in this blog) suggests that omicron9 replicates faster in the human bronchus and less in lung cells, which may explain its greater transmissibility and putative lower disease severity; although it remains unclear if these observations extend to rodents, we observed less infection of hamster bronchial cells in vivo with omicron than delta virus. Lower viral burden in nasal washes and turbinates in 129 mice were also measured comparing to other SARS-CoV-2 strains. The attenuation in mice was unexpected given that omicron has multiple mutations in the RBD that are sites associated with adaptation for mice.
Whereas the more than 30 substitutions in the omicron could impact receptor engagement and cell entry, sequence changes in other domains could affects replication, and so forth. Thus, detailed genetic and functional studies are required to define the basis of virological and clinical attenuation of omicron in mice and hamsters.

α-GalNAc is highly expressed on invasive cancer cells

A group from University of Oulu, Faculty of Biochemistry and Molecular Medicine, Oulu, Finland, etc. has reported that expression level of α-GalNAc recognized by Helix Pomatia agglutinin (HPA) lectin correlated significantly with invasive potential of cancer cells.

Authors investigated glycosylation profiles of the nine cancer cell lines with different invasiveness by using lectin microarray glycan profiling.

Out of 43 lectins in the lectin microarray, only five lectins (HPA, PTL-1, AJA, MAL I, PWM) were found to correlate either positively or negatively with the invasive potential of the cancer cells. Multiple linear regression analyses further demonstrated that these five lectins accounted for 97% of the variation observed in the cancer cell invasive phenotype, HPA alone accounted for 58% of the variation, and together with PTL-1, HPA accounted for 76% of the variation, while the rest (AJA, MAL I, PWM) correlated negatively and accounted for 7% each. Thus, increased expression of HPA-binding glycotopes (O-linked α-GalNAc) in cancer cells appears to be the main factor promoting cancer cell invasive phenotype.

Then, HPA-binding proteins were pulled down with HPA lectin, and identified with LC-MS/MS.

Of these, glycoproteins (EGFR, MMP-14, β4-, β1-, α2- and αV integrin) in HPA pulldown samples were markedly enriched in highly invasive cells relative to poorly invasive cells, indicating that these proteins carry increased levels of a terminal α-GalNAc in their glycans. Of these same glycoproteins, the EGFR and α2 integrin correlated significantly with cancer invasive potential.

Wheat rhizosphere: Bacillus velezensis improved salinity stress

A group from Key Laboratory of Biochemistry and Molecular Biology in University of Shandong Province, Weifang University, Weifang, China, etc. has reported Bacillus velezensis JC-K3 inoculation in wheat rhizosphere to improve salinity stress.

Soil salinity is one of the main manifestations of global land degradation. At present, at least 20% of the cultivated land in the world is threatened by salinization to varying degrees.

In this study, a strain of endophytic Bacillus velezensis JC-K3 was isolated from wheat grown on saline soils. This strain not only showed strong salt tolerance and alkali resistance, but also produced IAA, siderophore, proline, soluble sugar, protease, cellulase, and glucanase, which have the potential to improve plant salt tolerance and induce systemic tolerance. Actually, comparing with the control group, inoculation with endophytic Bacillus velezensis JC-K3 increased the accumulation of wheat biomass (the plant height increased by 12.69%, the root length increased by 27.59%, the fresh weight of wheat shoot increased by 13.55%) under the tested salinity stress (Salt tolerance (12% NaCl, w/v) was tested on DF agar medium supplemented with 1-aminocyclopropane-1-carboxylate).

There was no significant difference in the content of endophytic bacteria in wheat roots after JC-K3 inoculation when compared with the control. The contents of Cyanobacteria in the shoots of wheat were significantly decreased after inoculation with JC-K3 (p ≤ 0.001), while the contents of Proteobacteria, Actinobacteria, Chloroflexi, Bacteroidetes, Firmicutes, Gemmatimonadetes, Nitrospirae, Saccharibacteria, and Parcubacteria were significantly increased (p ≤ 0.001). The contents of Actinobacteria, Chloroflexi, Acidobacteria, Gemmatimonadetes, and Nitrospirae in wheat leaves were significantly increased after inoculation with JC-K3 (p ≤ 0.001). The content of Parcubacteria in rhizosphere soil decreased significantly (p ≤ 0.05).

After inoculation with JC-K3, there was no significant difference in the content of endophytic fungi in wheat roots and leaves. The content of Glomeromycota in wheat shoots decreased significantly (p ≤ 0.05), the content of Ascomycota in rhizosphere soil of wheat decreased significantly, and the content of Basidiomycota and Rozellomycota increased significantly (p ≤ 0.05).

SARS-CoV-2 Omicron diverged in early 2020, and evolved uniquely in a non-human?

A group from Research Institute of Public Health, Nankai University, Tianjin, PR China, etc. has reported on an origin of SARS-CoV-2 omicron variant.

Despite a large number of mutations in Omicron, no evidence was found in known public databases to suggest that these mutations slowly accumulated over time. Additionally, phylogenetic trees showed no intermediate branches of evolution, which is a very surprising result.

If Omicron evolved from a strain of the Delta variant, they would share a common mutation profile. However, analysis of data from GISAID showed that the Omicron variant differed from each of these strains and did not evolve from the Delta variant. The phylogenetic analysis strongly indicates that the Omicron variant forms a monophyletic group with the Gamma variant as a sister group, and the Omicron group has an extremely long branch length.
The time-scaled phylogenetic tree shows that the Omicron and Gamma lineages likely diverged in the first half of 2020. This supports the hypothesis that Omicron may have evolved in a non-human animal species. After accumulating many mutations in the animal host, the altered coronavirus was transmitted back to humans by reverse zoonosis.

Determining the origin of Omicron requires surveillance of animals, especially rodents, because they may have come into contact with humans carrying a strain of the virus with adaptive mutations.

A novel approach using glycoprotein targeted chimeric antigen receptor (CAR)-NK Cells for the treatment of SARS-CoV-2 infection

A group from The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA, etc. has reported a novel approach using glycoprotein targeted chimeric antigen receptor (CAR)-NK Cells for the treatment of SARS-CoV-2 infection.

NK cells are innate lymphocytes of the immune system with an important role in the control of viral infections, and CAR-T and CAR-NK cells are emerging immunotherapies against cancer and infectious disease with great promise.

Typically, the expressed synthetic receptors on NK cells are designed to bind target surface protein. In this study, authors designed a CAR making use of a unique extracellular moiety (i.e., lectin) with binding properties dependent on target glycosylation. Targeting of glycoprotein, and specifically N-glycosylation products, with a CAR is rare. This is the first CAR targeting the N-glycans dispersed on SARS-CoV-2 Spike protein, and also, this would be the first lectin-based CAR designed and functionally tested in pre-clinical study.

As lectins have evolved over millions of years to be highly potent and selective to glycans, the H84T-BanLec CAR represents an entirely new approach in that it targets aberrant glycosylation patterns (high mannose, in this case) in SARS-CoV-2 viral proteins. Here, Banlec is a lectin which is known to have binding specificity to high mannose which exists in proximity to the receptor binding domain of the envelope SARS-CoV-2 Spike protein.

There is a strong need for the development of CARs with receptor targeting patterns that are less likely to be impacted by genomic point mutations observed in RNA virus such as SARS-CoV-2.

relationship between wheat root rot disease and soil fungi

A group from Hubei Key Laboratory of Crop Disease, Insect Pests and Weeds Control, Wuhan, Hubei Province, China, etc. has reported about the relationship between wheat root rot disease and soil fungi.

There was a significant difference in abundance of fungi in the rhizosphere soil between healthy groups (H54 and H5) and diseased groups (D4 and D5) as shown below (with PCA analysis).

The genera with significant or extremely significant differences in richness among the above mentioned groups were Alternaria, Apodus, Epicoccum, Scytalidium and Chaetomium.
Alternaria: decrease in diseased states,
Apodus: increase in diseased states,
Epicoccum: decrease in diseased states,
Scytalidium: increase in diseased states, and
Chaetomium: increase in diseased state.

The existence of pathogenic fungi is a necessary condition for wheat root rot disease, but the richness of pathogenic fungi is not necessarily important. Based on the physical and chemical properties of the soil, an increase in NH4, NO3 and total nitrogen contributes to the occurrence of wheat root rot disease. Soil pH and soil density had the greatest influence on the abundance and diversity of rhizosphere fungi, and the influence was in the same direction; low soil pH and soil density are beneficial to the occurrence of wheat root rot disease.

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