Summary
SARS-CoV-2 Spike protein is critical for virus infection via engagement of ACE2
1
, and is a major antibody target. Here we report chronic SARS-CoV-2 with reduced sensitivity to neutralising antibodies in an immune suppressed individual treated with convalescent plasma, generating whole genome ultradeep sequences over 23 time points spanning 101 days. Little change was observed in the overall viral population structure following two courses of remdesivir over the first 57 days. However, following convalescent plasma therapy we observed large, dynamic virus population shifts, with the emergence of a dominant viral strain bearing D796H in S2 and ΔH69/ΔV70 in the S1 N-terminal domain NTD of the Spike protein. As passively transferred serum antibodies diminished, viruses with the escape genotype diminished in frequency, before returning during a final, unsuccessful course of convalescent plasma.
In vitro
, the Spike escape double mutant bearing ΔH69/ΔV70 and D796H conferred modestly decreased sensitivity to convalescent plasma, whilst maintaining infectivity similar to wild type. D796H appeared to be the main contributor to decreased susceptibility but incurred an infectivity defect. The ΔH69/ΔV70 single mutant had two-fold higher infectivity compared to wild type, possibly compensating for the reduced infectivity of D796H. These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy associated with emergence of viral variants with evidence of reduced susceptibility to neutralising antibodies.
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The phenolic compounds of 15 strawberry cultivars grown in Spain were analyzed and quantified: anthocyanins (20.2-47.4 mg/100 g of fw) (cyanidin 3-glucoside and pelargonidin 3-glucoside, 3-rutinoside, and 3-malonyl glucoside), flavonols (1.5-3.4 mg/100 g of fw) (quercetin 3-glucuronide and kaempferol 3-glucoside and 3-p-coumaroyl-glucoside), proanthocyanidins (53.9-163.2 mg/100 g), p-coumaroyl-glucose (0.84-6.70 mg/100 g), ellagitannins (9.67-22.86 mg/100 g) (sanguiin H-6, lambertianin C, and galloyl bis-HHDP-glucose), and ellagic acid glycosides (0.88-2.06 mg/100 g of fw) (two ellagic acid deoxyhexosides). Proanthocyanidins, the main phenolic compounds, were characterized by phloroglucinol degradation. Their mean degree of polymerization ranged from 3.4 for cv. Chiflon to 5.8 for cv. Ventana, the average value being 4.3. The terminal unit of proanthocyanidin oligomers was always (epi)catechin (17.36-29.93%) and (epi)catechin (61.66-75.39%) or (epi)afzelechin (4.50-10.54%) as extension units. Different combinations of (epi)catechin and (epi)afzelechin were detected, and their sequence of linkage was characterized by HPLC-MS-MS. Relative percentages of dimers, trimers, tetramers, and pentamers were evaluated by the extracted ion chromatogram (EIC) analysis.
A progressive displacement of tomato yellow leaf curl virus (TYLCV)-Sr by TYLCV-Is was observed in tomato epidemics in southern Spain based on incidence data of both virus species obtained during surveys conducted between 1996 and 1998. Ecological factors that might be involved in such a displacement, such as competition of TYLCV-Sr and TYLCV-Is in tomato, transmission by local biotypes (B and Q) of Bemisia tabaci, and presence in weeds and alternate crops, have been analyzed. No selective advantage is observed for TYLCV-Sr or TYLCV-Is in tomato plants either infected via Agrobacterium tumefaciens or via B. tabaci. However, TYLCV-Is is more efficiently vectored by local biotypes of B. tabaci; and common bean, a bridge crop between tomato crops, is a host for TYLCV-Is but not TYLCV-Sr. Therefore, common bean acts as a reservoir for TYLCV-Is. These two factors are probably responsible for the displacement of TYLCV-Sr by TYLCV-Is as the causative agent of epidemics in tomato in southern Spain.
This is a PDF file of a peer-reviewed paper that has been accepted for publication. Although unedited, the content has been subjected to preliminary formatting. Nature is providing this early version of the typeset paper as a service to our authors and readers. The text and figures will undergo copyediting and a proof review before the paper is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply.
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