Exploring the secrets of virus entry: the first respiratory syncytial virus carrying beta lactamase.

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Respiratory syncytial virus entry mechanism in host cells: A general overview.

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.

A Lachnospiraceae-dominated bacterial signature in the fecal microbiota of HIV-infected individuals from Colombia, South America.

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.