Anti-Human IAV H1N1 chimeric monoclonal antibody, clone Os9TB6

Influenza A virus (IAV) nonstructural protein 1 (NS1), a potent antagonist of the host immune response, is capable of interacting with RNA and a wide range of cellular proteins. NS1 consists of an RNA-binding domain (RBD) and an effector domain (ED) separated by a flexible linker region (LR). H5N1-NS1 has a characteristic 5-residue deletion in the LR, with either G (minor group) or E (major group) at the 71st position, and non-H5N1-NS1 contains E71 with an intact linker. Based on the orientation of the ED with respect to the RBD, previous crystallographic studies have shown that minor group H5N1-NS1(G71), a non-H5N1-NS1 [H6N6-NS1(E71)], and the LR deletion mutant H6N6-NS1(Delta 80-84/E71) mimicking the major group HSN1-NS1 exhibit "open," "semiopen," and "closed" conformations, respectively, suggesting that NS1 exhibits a strain-dependent conformational preference. Here we report the first crystal structure of a naturally occurring H5N1-NS1(E71) and show that it adopts an open conformation similar to that of the minor group of H5N1-NS1 [H5N1-NS1(G71)]. We also show that H6N6-NS1(Delta 80-84/E71) under a different crystallization condition and H6N6-NS1(Delta 80-84/G71) also exhibit open conformations, suggesting that NS1 can adopt an open conformation irrespective of E or G at the 71st position. Our single-molecule fluorescence resonance energy transfer (FRET) analysis to investigate the conformational preference of NS1 in solution showed that all NS1 constructs predominantly exist in an open conformation. Further, our coimmunoprecipitation and binding studies showed that they all bind to cellular factors with similar affinities. Taken together, our studies suggest that NS1 exhibits strain-independent structural plasticity that allows it to interact with a wide variety of cellular ligands during viral infection. IMPORTANCE IAV is responsible for several pandemics over the last century and continues to infect millions annually. The frequent rise in drug-resistant strains necessitates exploring novel targets for developing antiviral drugs that can reduce the global burden of influenza infection. Because of its critical role in the replication and pathogenesis of IAV, nonstructural protein 1 (NS1) is a potential target for developing antivirals. Previous studies suggested that NS1 adopts strain-dependent "open," "semiopen," and "closed" conformations. Here we show, based on three crystal structures, that NS1 irrespective of strain differences can adopt an open conformation. We further show that NS1 from different strains primarily exists in an open conformation in solution and binds to cellular proteins with a similar affinity. Together, our findings suggest that conformational polymorphism facilitated by a flexible linker is intrinsic to NS1, and this may be the underlying factor allowing NS1 to bind several cellular factors during IAV replication.

Facilities Management (FM) day-to-day tasks require suitable methods to facilitate work orders and improve performance by better collaboration between the office and the field. Building Information Modeling (BIM) provides opportunities to support collaboration and to improve the efficiency of Computerized Maintenance Management Systems (CMMSs) by sharing building information between different applications/users throughout the lifecycle of the facility. However, manual retrieval of building element information can be challenging and time consuming for field workers during FM operations. Mixed Reality (MR) is a visualization technique that can be used to improve visual perception of the facility by superimposing 3D virtual objects and textual information on top of the view of real-world building objects. This paper discusses the development of a collaborative BIM-based MR approach to support facilities field tasks. The proposed framework integrates multisource facilities information, BIM models, and feature-based tracking in an MR-based setting to retrieve information based on time (e.g. inspection schedule) and the location of the field worker, visualize inspection and maintenance operations, and support remote collaboration and visual communication between the field worker and the manager at the office. The field worker uses an Augmented Reality (AR) application installed on his/her tablet. The manager at the office uses an Immersive Augmented Virtuality (IAV) application installed on a desktop computer. Based on the field worker location, as well as the inspection or maintenance schedule, the field worker is given work orders and instructions from the office. Other sensory data (e.g., infrared thermography) can provide additional layers of information by augmenting the actual view of the field worker and supporting him/her in making effective decisions about existing and potential problems while communicating with the office in an Interactive Virtual Collaboration (IVC) mode. Finally, to investigate the applicability of the proposed method, a prototype system is developed and tested in a case study.