Single-dose vaccines with the ability to restrict SARS-CoV-2 replication in the respiratory tract are needed for all age groups, aiding efforts toward control of COVID-19. We developed a live intranasal vector vaccine for infants and children against COVID-19 based on replication-competent chimeric bovine/human parainfluenza virus type 3 (B/HPIV3) that express the native (S) or prefusion-stabilized (S-2P) SARS-CoV-2 S spike protein, the major protective and neutralization antigen of SARS-CoV-2. B/HPIV3/S and B/HPIV3/S-2P replicated as efficiently as B/HPIV3 in vitro and stably expressed SARS-CoV-2 S. Prefusion stabilization increased S expression by B/HPIV3 in vitro. In hamsters, a single intranasal dose of B/HPIV3/S-2P induced significantly higher titers compared to B/HPIV3/S of serum SARS-CoV-2–neutralizing antibodies (12-fold higher), serum IgA and IgG to SARS-CoV-2 S protein (5-fold and 13-fold), and IgG to the receptor binding domain (10-fold). Antibodies exhibited broad neutralizing activity against SARS-CoV-2 of lineages A, B.1.1.7, and B.1.351. Four weeks after immunization, hamsters were challenged intranasally with 104.5 50% tissue-culture infectious-dose (TCID50) of SARS-CoV-2. In B/HPIV3 empty vector-immunized hamsters, SARS-CoV-2 replicated to mean titers of 106.6 TCID50/g in lungs and 107 TCID50/g in nasal tissues and induced moderate weight loss. In B/HPIV3/S-immunized hamsters, SARS-CoV-2 challenge virus was reduced 20-fold in nasal tissues and undetectable in lungs. In B/HPIV3/S-2P–immunized hamsters, infectious challenge virus was undetectable in nasal tissues and lungs; B/HPIV3/S and B/HPIV3/S-2P completely protected against weight loss after SARS-CoV-2 challenge. B/HPIV3/S-2P is a promising vaccine candidate to protect infants and young children against HPIV3 and SARS-CoV-2.
The major tegument protein of bovine herpesvirus 1 (BoHV-1), VP8, is essential for virus replication in cattle. VP8 is phosphorylated in vitro by casein kinase 2 (CK2) and BoHV-1 unique short protein 3 (U S 3). In this study, VP8 was found to be phosphorylated in both transfected and infected cells but was detected as a nonphosphorylated form in mature virions. This suggests that phosphorylation of VP8 is strictly controlled during different stages of the viral life cycle. The regulation and function of VP8 phosphorylation by U S 3 and CK2 were further analyzed. An in vitro kinase assay, site-directed mutagenesis, and liquid chromatography-mass spectrometry were used to identify the active sites for U S 3 and CK2. The two kinases phosphorylate VP8 at different sites, resulting in distinct phosphopeptide patterns. S 16 is a primary phosphoreceptor for U S 3, and it subsequently triggers phosphorylation at S 32 . CK2 has multiple active sites, among which T 107 appears to be the preferred residue. Additionally, CK2 consensus motifs in the N terminus of VP8 are essential for phosphorylation. Based on these results, a nonphosphorylated VP8 mutant was constructed and used for further studies. In transfected cells phosphorylation was not required for nuclear localization of VP8. Phosphorylated VP8 appeared to recruit promyelocytic leukemia (PML) protein and to remodel the distribution of PML in the nucleus; however, PML protein did not show an association with nonphosphorylated VP8. This suggests that VP8 plays a role in resisting PML-related host antiviral defenses by redistributing PML protein and that this function depends on the phosphorylation of VP8. IMPORTANCEThe progression of VP8 phosphorylation over time and its function in BoHV-1 replication have not been characterized. This study demonstrates that activation of S 16 initiates further phosphorylation at S 32 by U S 3. Additionally, VP8 is phosphorylated by CK2 at several residues, with T 107 having the highest level of phosphorylation. Evidence for a difference in the phosphorylation status of VP8 in host cells and mature virus is presented for the first time. Phosphorylation was found to be a critical modification, which enables VP8 to attract and to redistribute PML protein in the nucleus. This might promote viral replication through interference with a PML-mediated antiviral defense. This study provides new insights into the regulation of VP8 phosphorylation and suggests a novel, phosphorylation-dependent function for VP8 in the life cycle of BoHV-1, which is important in view of the fact that VP8 is essential for virus replication in vivo. Bovine herpesvirus 1 (BoHV-1) is a herpesvirus belonging to the subfamily Alphaherpesvirinae and one of the most common pathogens in cattle. The major clinical symptoms caused by BoHV-1 are infectious bovine rhinotracheitis, conjunctivitis, vulvovaginitis, and balanoposthitis. The virus particle is composed of a capsid containing the double-stranded DNA genome, which is surrounded by a tegument layer and an en...
The outbreak of Coronavirus Disease 2019 (Covid-19) had an enormous impact on humanity. Till May 2021, almost 172 million people have been affected globally due to the contagious spread of Covid-19. Although the distribution of vaccines has been started, the worldwide mass distribution is yet to happen. According to the World Health Organization, wearing a facemask can reduce the contagious spread of Covid-19 significantly. The governments of different countries have recommended implementing the "no mask, no service" method to impede the spread of Covid-19. However, even the improper wearing of a facemask can obstruct the goal and lead to the spread of the virus. Therefore, to ensure public safety, a system for monitoring facemasks on faces, commonly known as a facemask detection algorithm, is essential for overcoming this crisis. The facemask detection algorithms are part of the object detection algorithms which are used to detect objects in an image. Among the various object detection algorithms, deep learning showed tremendous performance in facemask detection for its excellent feature extraction capability than the traditional machine learning algorithms. However, there remains a lot of scope for future research to build an efficient facemask detection system. Therefore, this study aims to draw attention to the researchers by providing a narrative and meta-analytic review on all the published works related to facemask detection in the context of Covid-19. Because facemask detection algorithms are run mainly by adopting object detection algorithms, this paper also explores the progress of object detection algorithms over the last few decades. A comprehensive analysis of different datasets used in facemask detection techniques by many studies has been explored. The performance comparison among these algorithms is discussed in narrative and meta-analytic approaches. Finally, this study concludes with a discussion of some of the major challenges and future scope in the related field.INDEX TERMS Covid-19, convolutional neural network, deep neural network, facemask detection, Covid-19 health, object detection, machine learning.
Anisotropic popcorn-shaped gold nanoparticles (GNPCs) were synthesized through a sustainable route. Proteins were used as ligands, and among several proteins, bovine serum albumin (BSA) produced high-quality GNPCs. The method is scalable to produce liters of NPs (with almost mM elemental Au concentration) in a single batch. Structural changes of proteins due to GNPC formation were studied in detail using circular dichroism and fluorescence spectroscopy. The secondary structure of proteins was lost in the growth step, which facilitates the formation of GNPCs. Among other similar sized gold nanoparticles, GNPC@BSA was found to have high colloidal stability and biocompatibility.
The polymorphisms of invasion suppressor gene CDH1 and DNA mismatch repair gene Exo1 have been reported to play critical role in the development, tumorigenesis, and progression of several kinds of cancers including prostate cancer. This study was designed to analyze the contribution of single-nucleotide polymorphisms of the CDH1 (-160C/A) and Exo1 (K589E) to prostate cancer susceptibility in Bangladeshi population. The study included 100 prostate cancer cases and age-matched 100 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to determine the genetic polymorphisms. A significant association was found between CDH1 -160C/A (rs16260) and Exo1 (rs1047840, K589E) polymorphisms and prostate cancer risk. In case of CDH1 -160C/A polymorphism, the frequencies of the three genotypes C/C,C/A, and A/A were 45%, 48%, and 7% in cases and 63%, 32%, and 5% in controls, respectively. The heterozygote C/A genotype and combined C/A+A/A genotypes showed 2.10-fold (odds ratio = 2.1000, 95% confidence interval = 1.2956-4.0905, p = 0.013) and 2.08-fold (odds ratio = 2.0811, 95% confidence interval = 1.1820-3.6641, p = 0.011) increased risk of prostate cancer, respectively, when compared with homozygous C/C genotypes. The variant A allele also was associated with increased risk of prostate cancer (odds ratio = 1.6901, 95% confidence interval = 1.0740-2.6597, p = 0.0233). In case of Exo1 (K589E) polymorphism, G/A heterozygote, A/A homozygote, and combined G/A+A/A genotypes were found to be associated with 2.30-, 4.85-, and 3.04-fold higher risk of prostate cancer, respectively (odds ratio = 2.3021, 95% confidence interval = 2.956-4.0905, p = 0.0031; odds ratio = 4.8462, 95% confidence interval = 1.0198-23.0284, p = 0.0291; OR = 3.0362, 95% confidence interval = 1.7054-5.4053, p = 0.0001, respectively). The ''A'' allele showed significant association with increased susceptibility (2.29-fold) to prostate cancer (odds ratio = 2.2955, 95% confidence interval = 1.4529-3.6270, p = 0.0004). Our results suggest that CDH1 -160C/A and Exo1 K589E polymorphisms are associated with increased susceptibility to prostate cancer in Bangladeshi population.
The U L 47 gene product, VP8, is the most abundant tegument protein of bovine herpesvirus 1 (BoHV-1). Previously, we demonstrated that a U L 47-deleted BoHV-1 mutant (BoHV1-⌬U L 47) exhibits 100-fold-reduced virulence in vitro and is avirulent in vivo. In this study, we demonstrated that VP8 expression or BoHV-1 infection inhibits interferon beta (IFN-) signaling by using an IFN-␣/-responsive plasmid in a luciferase assay. As transducer and activator of transcription (STAT) is an essential component in the IFN-signaling pathways, the effect of VP8 on STAT was investigated. An interaction between VP8 and STAT1 was established by coimmunoprecipitation assays in both VP8-transfected and BoHV-1-infected cells. Two domains of VP8, amino acids 259 to 482 and 632 to 686, were found to be responsible for its interaction with STAT1. The expression of VP8 did not induce STAT1 ubiquitination or degradation. Moreover, VP8 did not reduce STAT1 tyrosine phosphorylation to downregulate IFN- signaling. However, the expression of VP8 or a version of VP8 (amino acids 219 to 741) that contains the STAT1-interacting domains but not the nuclear localization signal prevented nuclear accumulation of STAT1. Inhibition of nuclear accumulation of STAT1 also occurred during BoHV-1 infection, while nuclear translocation of STAT1 was observed in BoHV1-⌬U L 47-infected cells. During BoHV-1 infection, VP8 was detected in the cytoplasm at 2 h postinfection without any de novo protein synthesis, at which time STAT1 was already retained in the cytoplasm. These results suggest that viral VP8 downregulates IFN- signaling early during infection, thus playing a role in overcoming the antiviral response of BoHV-1-infected cells. IMPORTANCESince VP8 is the most abundant protein in BoHV-1 virions and thus may be released in large amounts into the host cell immediately upon infection, we proposed that it might have a function in the establishment of conditions suitable for viral replication. Indeed, while nonessential in vitro, it is critical for BoHV-1 replication in vivo. In this study, we determined that VP8 plays a role in downregulation of the antiviral host response by inhibiting IFN- signaling. VP8 interacted with and prevented nuclear accumulation of STAT1 at 2 h postinfection in the absence of de novo viral protein synthesis. Two domains of VP8, amino acids 259 to 482 and 632 to 686, were found to be responsible for this interaction. These results provide a new functional role for VP8 in BoHV-1 infection and a potential explanation for the lack of viral replication of the U L 47 deletion mutant in cattle. Bovine herpesvirus 1 (BoHV-1) is responsible for several clinical manifestations, including rhinotracheitis, vulvovaginitis, and conjunctivitis, in cattle (1). BoHV-1 is composed of a doublestranded DNA surrounded by a nucleocapsid, a tegument, and an envelope (2). Although the tegument is a major constituent in the BoHV-1 virion, it is the least studied. The tegument consists of at least 20 virus-encoded proteins (reviewed in ref...
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