Respiratory syncytial virus (RSV) is a virus that causes acute respiratory infections in neonates and older adults. To infect host cells, the attachment glycoprotein (G) interacts with a cell surface ...receptor. This interaction determines the specific cell types that are susceptible to infection. RSV possesses a type I fusion protein F. Type I fusion proteins are metastable when rearrangement of the prefusion F occurs; the fusion peptide is exposed transforming the protein into postfusion form. The transition between the prefusion form and its postfusion form facilitates the viral envelope and the host cell membrane to fuse, enabling the virus to enter the host cell. Understanding the entry mechanism employed by RSV is crucial for developing effective antiviral therapies. In this review, we will discuss the various types of viral fusion proteins and explore the potential entry mechanisms utilized by RSV. A deeper understanding of these mechanisms will provide valuable insights for the development of novel approaches to treat RSV infections.
Respiratory syncytial virus (RSV) infection is one of the major causes of respiratory tract infection for which no vaccine or antiviral treatment is available. The RSV NS1 protein seems to antagonize ...the host interferon (IFN) response; however, its mechanism is unknown. Here, we used a plasmid-borne small interfering RNA targeting the NS1 gene (siNS1) to examine the role of NS1 in modulating RSV infection. RSV replication was reduced in A549 cells, but not IFN-deficient Vero cells, transfected with siNS1. siNS1 induced upregulated expression of IFN-beta and IFN-inducible genes in A549 cells. siNS1-transfected human dendritic cells, upon RSV infection, produced elevated type-1 IFN and induced differentiation of naive CD4+ T cells to T helper type 1 (TH1) cells. Mice treated intranasally with siNS1 nanoparticles before or after infection with RSV showed substantially decreased virus titers in the lung and decreased inflammation and airway reactivity compared to controls. Thus, siNS1 nanoparticles may provide an effective inhibition of RSV infection in humans.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Andrographolide (
1
), the major labdane diterpenoidal constituent of
Andrographis paniculata
Wall, has been found to be majorly responsible for the medicinal uses of the plant particularly ...anti-cancer properties. In our previous work, we have found 3,19-diacetyl-12-phenylthio-14-deoxy-andrographolide (
3g),
a semi-synthetic derivative of Andrographolide to be one of the most potent compounds exhibiting cytotoxic activity against a number of human cancer cell lines particularly HCT-116 cell line. In this work, we report the effect of
3g
on cell cycle arrest and its apoptosis inducing potential on HCT-116 cell line. In addition, we also report the synthesis of some new 3,19-diacetyl-
C
-12-substituted-14-deoxy-andrographolide derivatives
3a–f,
their cytotoxic effects on colon cancer cells (HCT-116), and the mechanistic studies of the active analogue
3c
. Encouragingly, we have also found that the compounds
3c
and
3g
were observed to be non-toxic (IC
50
> 250 μM) to baby hamster kidney (BHK-21) normal cells.
Tuberculosis continues to be a great source of concern in global health because of the large reservoir of humans infected with the bacilli and the appearance of clinical isolates resistant to a wide ...array of anti-tuberculosis drugs. New drugs with novel mechanisms of action on new targets are urgently required to reduce global tuberculosis burden.
nucleoid associated protein (NAP) HU has been shown to be druggable and essential for the organism's survival. In this study, four diarylethenes were synthesized using a one-pot decarboxylated Heck-coupling of coumaric acids with iodoanisoles. The prepared compounds
-
were tested for their in vitro growth inhibition of
H37Rv using the spot culture growth inhibition assay, displaying minimum inhibitory concentrations between 9 and 22 µM. Their cytotoxicity against BHK-21 cell line showed half inhibition at concentrations between 98 and 729 µM. The most selective hit (SI = 81), demonstrated inhibition of
HU protein involved in maintaining bacterial genome architecture.
Introducción. El virus sincicial respiratorio humano (hRSV) es la causa más frecuente de infección respiratoria aguda de las vías respiratorias inferiores en niños menores de cinco años. El ...desarrollo de técnicas moleculares para identificarlo es uno de los retos actuales en el campo de la investigación clínica.Objetivo. Evaluar un método de amplificación isotérmica para la detección rápida del hRSV en niños con infección respiratoria aguda.Materiales y métodos. Se extrajo el ARN viral de 304 muestras de hisopado nasal en niños con síntomas de infección respiratoria aguda atendidos en el servicio de urgencias del Hospital de la Universidad del Norte en Barranquilla entre abril del 2016 y julio del 2017. Se evaluó la prueba de amplificación isotérmica mediada por bucle mediante transcriptasa inversa de la proteína de la matriz (M) (Reverse Transcription Loop-Mediated Isothermal Amplification, RT-LAMP) comparada con técnicas moleculares como la reacción en cadena de la polimerasa mediante transcriptasa inversa múltiple anidada (Reverse Transcription-Polymerase Chain Reaction, RT-PCR), la cual se empleó como la prueba estándar, la PCR en tiempo real (quantitative PCR, qPCR) y la RT-LAMP de la proteína L (L) para la detección rápida del virus sincicial respiratorio (VSR), subtipo A y subtipo B.Resultados. La prueba de RT-LAMP (M) tuvo una sensibilidad de 93,59 %, una especificidad de 92,92 % y una concordancia de 0,83 ± 0,036 comparada con la prueba de RT-PCR anidada. El índice kappa del RT-LAMP (M) fue superior, y los valores del RTLAMP (L) y la qPCR concordaron (0,75 ± 0,043 y 0,71 ± 0,045, respectivamente).
Respiratory syncytial virus (RSV) nonstructural protein 1(NS1) attenuates type-I interferon (IFN) production during RSV infection; however the precise role of RSV NS1 protein in orchestrating the ...early host-virus interaction during infection is poorly understood. Since NS1 constitutes the first RSV gene transcribed and the production of IFN depends upon RLR (RIG-I-like receptor) signaling, we reasoned that NS1 may interfere with this signaling. Herein, we report that NS1 is localized to mitochondria and binds to mitochondrial antiviral signaling protein (MAVS). Live-cell imaging of rgRSV-infected A549 human epithelial cells showed that RSV replication and transcription occurs in proximity to mitochondria. NS1 localization to mitochondria was directly visualized by confocal microscopy using a cell-permeable chemical probe for His(6)-NS1. Further, NS1 colocalization with MAVS in A549 cells infected with RSV was shown by confocal laser microscopy and immuno-electron microscopy. NS1 protein is present in the mitochondrial fraction and co-immunoprecipitates with MAVS in total cell lysatesof A549 cells transfected with the plasmid pNS1-Flag. By immunoprecipitation with anti-RIG-I antibody, RSV NS1 was shown to associate with MAVS at an early stage of RSV infection, and to disrupt MAVS interaction with RIG-I (retinoic acid inducible gene) and the downstream IFN antiviral and inflammatory response. Together, these results demonstrate that NS1 binds to MAVS and that this binding inhibits the MAVS-RIG-I interaction required for IFN production.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The first cases of Zika virus infection in Colombia were reported and confirmed in October 2015. The objective of the study was estimate the seroprevalence of ZIKV infection during the pre-epidemic ...phase in Barranquilla, Colombia, and demonstrate the presence of virus before the Colombian Ministry of Health confirmed the first case. We conducted a descriptive study of the seroprevalence of Zika virus in 390 samples obtained from a blood bank located in Barranquilla, Colombia - a city endemic for dengue, and with a recent history of a Chikungunya disease epidemic. The serum pools were tested using Euroimmun ZIKV ELISA kit. Seroprevalence of Zika virus IgG were: May 2015: 0%, June and July 2015: 2.62% (95% CI = 0.28-12.13) and August 2015: 5.35% (95% CI = 1.74-16.74). This brings to our attention the need for extending the surveillance period of this virus in order to adequately assess its teratogenic effects.
Respiratory Syncytial Virus (RSV) presents a significant health threat, especially to young children. In-depth understanding of RSV entry mechanisms is essential for effective antiviral development. ...This study introduces an innovative RSV variant, featuring the fusion of the beta-lactamase (BlaM) enzyme with the RSV-P phosphoprotein, providing a versatile tool for dissecting viral entry dynamics.
Using the AlphaFold2 algorithm, we modeled the tertiary structure of the P-BlaM chimera, revealing structural similarities with both RSV-P and BlaM. Functional assessments, utilizing flow cytometry, quantified beta-lactamase activity and GFP expression in infected bronchial epithelial cells. Western blot analysis confirmed the integrity of P-BlaM within virions.
The modeled P-BlaM chimera exhibited structural parallels with RSV-P and BlaM. Functional assays demonstrated robust beta-lactamase activity in recombinant virions, confirming successful P-BlaM incorporation as a structural protein. Quercetin, known for its antiviral properties, impeded viral entry by affecting virion fusion. Additionally, Ulixertinib, an ERK-1/2 inhibitor, significantly curtailed viral entry, implicating ERK-1/2 pathway signaling.
Our engineered RSV-P-BlaM chimera emerges as a valuable tool, illuminating RSV entry mechanisms. Structural and functional analyses unveil potential therapeutic targets. Quercetin and Ulixertinib, identified as distinct stage inhibitors, show promise for targeted antiviral strategies. Time-of-addition assays pinpoint quercetin's specific interference stage, advancing our comprehension of RSV entry and guiding future antiviral developments.
Severe lower respiratory tract infection in infants and young children is most frequently caused by respiratory syncytial virus (RSV). RSV infects the smallest airways, making breathing difficult and ...in some infants requiring medical support. Severity is affected by viral dose, infant age, virus genotype, and effectiveness of the innate/adaptive immune responses. Severe disease correlates with later wheezing and asthma in some children. The adaptive immune response is protective but wanes after each infection, likely due to the ability of the RSV NS1/NS2 proteins to inhibit the innate immune response. Several vaccine approaches and candidates are currently in clinical trials.
HIV infection has a tremendous impact on the immune system's proper functioning. The mucosa-associated lymphoid tissue (MALT) is significantly disarrayed during HIV infection. Compositional changes ...in the gut microbiota might contribute to the mucosal barrier disruption, and consequently to microbial translocation. We performed an observational, cross-sectional study aimed at evaluating changes in the fecal microbiota of HIV-infected individuals from Colombia. We analyzed the fecal microbiota of 37 individuals via 16S rRNA gene sequencing; 25 HIV-infected patients and 12 control (non-infected) individuals, which were similar in body mass index, age, gender balance and socioeconomic status. To the best of our knowledge, no such studies have been conducted in Latin American countries. Given its compositional nature, microbiota data were normalized and transformed using Aitchison's Centered Log-Ratio. Overall, a change in the network structure in HIV-infected patients was revealed by using the SPIEC-EASI MB tool. Genera such as Blautia, Dorea, Yersinia, Escherichia-Shigella complex, Staphylococcus, and Bacteroides were highly relevant in HIV-infected individuals. Differential abundance analysis by both sparse Partial Least Square-Discriminant Analysis and Random Forest identified a greater abundance of Lachnospiraceae-OTU69, Blautia, Dorea, Roseburia, and Erysipelotrichaceae in HIV-infected individuals. We show here, for the first time, a predominantly Lachnospiraceae-based signature in HIV-infected individuals.
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