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6% (13/63). HBeAgNeg patients with low levels of HBsAg (log IU ≤ 3) were older and were characterized by undetectable plasma HBV-DNA and undetectable HBV-RNA but not undetectable HBV-DNA in PBMCs compared to those with high HBsAg levels. In >50% of the studied HBeAgNeg patients (66/126), the quantitation of HBsAg and HBV-RNA may impact clinical decisions. In conclusion, the combined assessment of classical and novel serum biomarkers, especially in HBeAgNeg patients, which is the largest group of CHB patients in many regions, may assist in clinical decisions. Prospective studies are required to determine the real-time additive clinical advantage of these biomarkers.Scribble is a highly conserved regulator of cell polarity, a process that enables the generation of asymmetry at the cellular and tissue level in higher organisms. Scribble acts in concert with Disc-large (Dlg) and Lethal-2-giant larvae (Lgl) to form the Scribble polarity complex, and its functional dysregulation is associated with poor prognosis during viral infections. Viruses have been shown to interfere with Scribble by targeting Scribble PDZ domains to subvert the network of interactions that enable normal control of cell polarity via Scribble, as well as the localisation of the Scribble module within the cell. The influenza A virus NS1 protein was shown to bind to human Scribble (SCRIB) via its C-terminal PDZ binding motif (PBM). It was reported that the PBM sequence ESEV is a virulence determinant for influenza A virus H5N1 whilst other sequences, such as ESKV, KSEV and RSKV, demonstrated no affinity towards Scribble. We now show, using isothermal titration calorimetry (ITC), that ESKV and KSEV bind to SCRIB PDZ domains and that ESEV unexpectedly displayed an affinity towards all four PDZs and not just a selected few. We then define the structural basis for the interactions of SCRIB PDZ1 domain with ESEV and ESKV PBM motifs, as well as SCRIB PDZ3 with the ESKV PBM motif. These findings will serve as a platform for understanding the role of Scribble PDZ domains and their interactions with different NS1 PBMs and the mechanisms that mediate cell polarity within the context of the pathogenesis of influenza A virus.Our paper presents detailed evolutionary analyses of narcissus viruses from wild and domesticated Narcissus plants in Japan. Narcissus late season yellows virus (NLSYV) and narcissus degeneration virus (NDV) are major viruses of Narcissus plants, causing serious disease outbreaks in Japan. In this study, we collected Narcissus plants showing mosaic or striped leaves along with asymptomatic plants in Japan for evolutionary analyses. Our findings show that (1) NLSYV is widely distributed, whereas the distribution of NDV is limited to the southwest parts of Japan; (2) the genomes of NLSYV isolates share nucleotide identities of around 82%, whereas those of NDV isolates are around 94%; (3) three novel recombination type patterns were found in NLSYV; (4) NLSYV comprises at least five distinct phylogenetic groups whereas NDV has two; and (5) infection with narcissus viruses often occur as co-infection with different viruses, different isolates of the same virus, and in the presence of quasispecies (mutant clouds) of the same virus in nature. Therefore, the wild and domesticated Narcissus plants in Japan are somewhat like a melting pot of potyviruses and other viruses.
Trentino is an Italian province with a tourism-based economy, bordering the regions of Lombardy and Veneto, where the two earliest and largest outbreaks of COVID-19 occurred in Italy. The earliest cases in Trentino were reported in the first week of March 2020, with most of the cases occurring in the winter sport areas in the Dolomites mountain range. The number of reported cases decreased over the summer months and was followed by a second wave in the autumn and winter of 2020.
we performed high-coverage Oxford Nanopore sequencing of 253 positive SARS-CoV-2 swabs collected in Trentino between March and December 2020.
in this work, we analyzed genome sequences to trace the routes through which the virus entered the area, and assessed whether the autumnal resurgence could be attributed to lineages persisting undetected during summer, or as a consequence of new introductions.
Comparing the draft genomes analyzed with a large selection of European sequences retrieved from GISAID we found that multiple introductions of the virus occurred at the early stage of the epidemics; the two epidemic waves were unrelated; the second wave was due to reintroductions of the virus in summer when traveling restrictions were uplifted.
Comparing the draft genomes analyzed with a large selection of European sequences retrieved from GISAID we found that multiple introductions of the virus occurred at the early stage of the epidemics; the two epidemic waves were unrelated; the second wave was due to reintroductions of the virus in summer when traveling restrictions were uplifted.Since the 2014-2016 epidemic, Ebola virus (EBOV) has spread to several countries and has become a major threat to global health. Daclatasvir order EBOV is a risk group 4 pathogen, which imposes significant obstacles for the development of countermeasures against the virus. Efforts have been made to develop anti-EBOV immunization and therapeutics, with three vaccines and two antibody-based therapeutics approved in recent years. Nonetheless, the high fatality of Ebola virus disease highlights the need to continuously develop antiviral strategies for the future management of EBOV outbreaks in conjunction with vaccination programs. This review aims to highlight potential EBOV therapeutics and their target(s) of inhibition, serving as a summary of the literature to inform readers of the novel candidates available in the continued search for EBOV antivirals.The Human Immunodeficiency Virus and retroviral therapy are both known risk factors for cardiovascular disease. It remains an open question whether HIV or ARV leads to increased arterial inflammation. The objective of this study was to investigate the changes in endothelial activation by measuring VCAM-1 levels among HIV-infected patients who were and were not treated with antiretroviral therapy. It is a retrospective study that included 68 HIV-infected patients, 23 of whom were never antiretroviral-treated, 15 who were ART-treated for no longer than a year, and 30 who were ART-treated for longer than a year. Blood samples were collected for biochemical analysis of the concentration of VCAM-1. The results show a statistically lower VCAM-1 level (p = 0.007) in patients treated with ART longer than a year (1442 ng/mL) in comparison to treatment-naïve patients (2392 ng/mL). The average VCAM-1 level in patients treated no longer than a year (1552 ng/mL) was also lower than in treatment-naïve patients, but with no statistical significance (p = 0.096). Long-term antiretroviral therapy was associated with the decline of VCAM-1 concentration. That may suggest the lowering of endothelial activation and the decreased risk of the development of cardiovascular disease among ARV-treated patients. However, VCAM-1 may not be a sufficient factor itself to assess this, since simultaneously there are a lot of well-known cardiovascular-adverse effects of ART.In December 2020, WHO presented the first international standard (WHO IS) for anti-SARS-CoV-2 immunoglobulin. This standard is intended to serve as a reference reagent against which serological tests can be calibrated, thus creating better comparability of results between different tests, laboratories, etc. Here, we have examined three different commercial ELISA kits for the quantification of SARS-CoV-2 IgG antibodies, namely the Anti-SARS-CoV-2 QuantiVac ELISA (IgG) (Euroimmun, Lübeck, Germany), the SERION ELISA agile (Institut Virion Serion, Würzburg, Germany), and the COVID-19 quantitative IgG ELISA (DeMediTec Diagnostics, Kiel, Germany). According to the manufacturers, all are calibrated against the WHO IS and can provide results in either international units (IU) (DeMediTec) or arbitrary antibody units (BAU) per milliliter (Euroimmun, Virion Serion), which are numerically identical, according to the WHO. A total of 50 serum samples from vaccinated individuals were tested side by side and according to the manufacturer's instructions. We compared the test results of all three assays with each other to assess comparability and with a quantitative in-house virus neutralization test (micro-NT). In summary, our data are consistent with other studies published on this topic that tested similar assays from different manufacturers. Overall, the agreement between quantitative ELISAs is variable and cannot be used interchangeably despite calibration against a standard. Therefore, interpretation of results must still be individualized and tailored to each case. More importantly, our results highlight that quantitative ELISAs in their current form cannot replace neutralization tests.Apple rubbery wood virus 2 (ARWV-2) and citrus virus A (CiVA) belong to a recently approved family Phenuiviridae in the order Bunyavirales and possess negative-sense single-stranded RNA genomes. In this study, the genome sequence of three ARWV-2 isolates (S17E2, LYC2, and LYXS) and a CiVA isolate (CiVA-P) infecting pear trees grown in China were characterized using high-throughput sequencing combined with conventional reverse-transcription PCR (RT-PCR) assays. The genome-wide nt sequence identities were above 93.6% among the ARWV-2 isolates and above 93% among CiVA isolates. Sequence comparisons showed that sequence diversity occurred in the 5' untranslated region of the ARWV-2 genome and the intergenic region of the CiVA genome. For the first time, this study revealed that ARWV-2 proteins Ma and Mb displayed a plasmodesma subcellular localization, and the MP of CiVA locates in cell periphery and can interact with the viral NP in bimolecular fluorescence complementation assays. RT-PCR tests disclosed that ARWV-2 widely occurs, while CiVA has a low incidence in pear trees grown in China. This study presents the first complete genome sequences and incidences of ARWV-2 and CiVA from pear trees and the obtained results extend our knowledge of the viral pathogens of pear grown in China.African swine fever is one of the most devastating swine diseases caused by African swine fever virus (ASFV). Although ASFV encodes more than 160 viral proteins, the implication of a majority of ASFV proteins in regulating host immunity is yet to be explored, and the mechanisms of immune evasion by ASFV proteins are largely unknown. Here, we report that the I226R protein of ASFV significantly suppressed innate immune responses. The ectopic expression of ASFV I226R in 293T cells significantly inhibited the activation of interferon-stimulated response element promoters triggered by Sendai virus (SeV), poly(IC), or cyclic GMP-AMP synthase (cGAS)/STING. The I226R protein caused a significant decrease in the expression of interferons and interferon-stimulating genes in cells infected with SeV. Similar results were obtained from experiments using I226R-overexpressed PK15 and 3D4/21 cells stimulated with vesicular stomatitis virus. We observed that I226R inhibited the activation of both nuclear factor-kappa B (NF-κB) and interferon regulatory factor 3 (IRF3).