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Oropouche orthobunyavirus (OROV; Peribunyaviridae ) is a mosquito-transmitted virus that causes widespread human febrile illness in South America, with occasional progression to neurologic effects. Host factors mediating the cellular entry of OROV are undefined. Here, we show that OROV uses the host protein low-density lipoprotein–related protein 1 (Lrp1) for efficient cellular infection. Cells from evolutionarily distinct species lacking Lrp1 were less permissive to OROV infection than cells with Lrp1. Treatment of cells with either the high-affinity Lrp1 ligand receptor-associated protein (RAP) or recombinant ectodomain truncations of Lrp1 significantly reduced OROV infection. In addition, chimeric vesicular stomatitis virus (VSV) expressing OROV glycoproteins (VSV-OROV) bound to the Lrp1 ectodomain in vitro. Furthermore, we demonstrate the biological relevance of the OROV-Lrp1 interaction in a proof-of-concept mouse study in which treatment of mice with RAP at the time of infection reduced tissue viral load and promoted survival from an otherwise lethal infection. These results with OROV, along with the recent finding of Lrp1 as an entry factor for Rift Valley fever virus, highlight the broader significance of Lrp1 in cellular infection by diverse bunyaviruses. Shared strategies for entry, such as the critical function of Lrp1 defined here, provide a foundation for the development of pan-bunyaviral therapeutics.

Tuberculosis remains a serious global health problem. BCG is the only prophylactic TB vaccine and it shows variable protective efficacy. Chimeric protein subunit vaccines hold great potential as stand-alone vaccines or heterologous BCG prime boosters. We have designed a protein chimera, PP31, by combining Mtb ESAT-6 family antigen Rv1198 and MoCo biosynthesis family antigen Rv3111. Further, PP31 was extended by addition of latency antigen Rv1813c to yield PP43. Immunization of BALB/c mice with PP31 or PP43 with FIA adjuvant elicited strong humoral immune response. Restimulation of splenocytes of the immunized mice lead to significant proliferation of lymphocytes, secretion of cytokines IFN-γ, TNF, IL-2 of the Th1 class, IL-17A of the Th17 class, and IL-6. PP31 and PP43 also induced intracellular cytokine expression (IFN-γ, TNF, and IL-2) from both CD4+-CD44high and CD8+-CD44high T-cells. Antigen-specific IFN-γ+/IL-2+ double positive CD4+ T-cells were significantly higher in case of PP43 than PP31-immunized mice and control group. PP43 showed protection equivalent to heat-inactivated BCG in response to challenge of the immunized mice with Mtb H37Ra. Based on its immunogenicity and protective efficacy, PP43 appears to be a potential candidate for further development as a subunit vaccine against TB.

The ESAT-6 family proteins of Mycobacterium tuberculosis are regarded as the key mediators in mycobacterial virulence and are largely considered as antigens that can improve TB vaccines and diagnostics. We have characterized Rv3444c and Rv3445c proteins of the ESX-4 system of ESAT-6 family of M. tuberculosis H37Rv, and have experimentally established that these two proteins interact to form a heterodimeric complex. Complex formation resulted in induction of α-helical conformation and stability against chemical denaturation. To evaluate the immunogenic potential, we have immunized mice with Rv3444c or Rv3445c along with Freund's incomplete adjuvant (FIA). Immunization with Rv3444c-FIA or Rv3445c-FIA resulted in long term humoral responses. Re-stimulation of splenocytes from immunized mice resulted in significant lymphocyte proliferation with induction of TNF-α and IL-6. Further, the humoral responses to Rv3444c and Rv3445c antigens in Indian patients with active pulmonary TB (n = 44), and healthy individuals (n = 20), were investigated. Compared to healthy individuals, high levels of IgG against Rv3444c and Rv3445c were observed in TB patient's sera, indicating that these proteins are actively produced during the active phase of TB. Cellular immune responses to these proteins in active pulmonary TB patients (n = 5) were also investigated using peripheral blood mononuclear cells (PBMCs). Both the proteins induce significant lymphocyte proliferation and up-regulate the induction of TNF-α and IL-6 in TB patients.

Today's world emphasizes a lot on speed, performance and ease of use. Taking these demands into consideration it has become mandatory to change all existing systems and transform them into ones that can deliver these characteristics. One such system has been network architecture. Since many years' vendors have been creating and developing their own Network Infrastructure, with different policies and different instruction sets. But communication between networks has taken up importance so as to reduce the timing taken by the data packet to pass through the security settings of another network and vice versa. Hence here is where Interoperability comes into play. If we can take all the networks and have a common controller for all the networks, it would reduce the time and complexity for communicating between them. A simple way to achieve it is through Software Defined Networking, where we can use the software to control the flow of data packets as well as monitor the network. Software Defined Networking is a networking prototype which allows network operators to manage networking elements using software running on an external server. This is accomplished by a split in the architecture between the forwarding element and the control element. The traditional network tends to be rigid. Once the forwarding policy has been defined, the only way to change it is by changing the configuration of all the affected devices.This is time consuming and puts a limit on scalability and meeting challenges of mobility and big data. In this context software defined networking SDN is being looked upon as a promising paradigm that has the power to change the way networking is done. By centralizing control, and making forwarding nodes simple, SDN offers flexible control over the traffic flows and the policies networks use to manage these flows. Along with the excitement, there have been apprehensions regarding SDN. In any organization, actual network is not confined to simple configuration. The real network configurations in these organizations are complex and represent more like bulky connectivity. The designing of custom network is done on the GNS3 platform. It is python based and the configurations on GNS3 can be moved to real world networks with minimal changes. The custom network refers to the configuration of network according to ones need and requirement. That means that number of router, switches and links are not defined, they may change as per the need. The various components of the SDN network is then studied in both the traditional and custom network. The adoption of SDN has still not done in physical network. There have been a number of trial deployments but very few production networks. In this paper, we would discuss the important implementation issues in SDN, the requirements it would fulfill in two fast growing areas wireless networks and clouds and the research that is taking place in these areas. We discuss, in some detail, the enrichments required in the SDN framework as far as security is concerned. Finally, we explore the future directions that SDN research is expected to take. The biggest benefit of Open Flow is to decouple the control plane from the data plane, allowing the centralized forwarding decisions in comparison to traditional distributed control network. As a result, we propose a Software Defined coding network and address key technical challenges in practice. Farheen Fatma Ansari | Prof. Sumit Kumar Sar | Prof. D. P. Mishra "A Study and Designing of Custom Network Configuration using Integrated Protocols in SDN Architecture" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-2 | Issue-4 , June 2018, URL: https://www.ijtsrd.com/papers/ijtsrd14458.pdf

Background Accumulation of toxic peptidyl-tRNAs in the bacterial cytoplasm is averted by the action of peptidyl-tRNA hydrolase (Pth), which cleaves peptidyl-tRNA into free tRNA and peptide. NMR studies are needed for a protein homolog with a complete crystal structure, for comparison with the NMR structure of Mycobacterium tuberculosis Pth. Methods The structure and dynamics of Mycobacterium smegmatis Pth (MsPth) were characterized by NMR spectroscopy and MD simulations. The thermal stability of MsPth was characterized by DSC. Results MsPth NMR structure has a central mixed seven stranded β-sheet that is enclosed by six α-helices. NMR relaxation and MD simulations studies show that most of the ordered regions are rigid. Of the substrate binding segments, the gate loop is rigid, the base loop displays slow motions, while the lid loop displays fast timescale motions. MsPth displays high thermal stability characterized by a melting temperature of 61.71 °C. Conclusion The NMR structure of MsPth shares the canonical Pth fold with the NMR structure of MtPth. The motional characteristics for the lid region, the tip of helix α3, and the gate region, as indicated by MD simulations and NMR data, are similar for MsPth and MtPth. However, MsPth has relatively less rigid base loop and more compactly packed helices α5 and α6. The packing and the dynamic differences appear to be an important contributing factor to the thermal stability of MsPth, which is significantly higher than that of MtPth. Significance MsPth structure consolidates our understanding of the structure and dynamics of bacterial Pth proteins.