Molecular Mimicry as a Mechanism of Viral Immune Evasion and Autoimmunity.

Mimicry of host protein structures ("molecular mimicry") is a common mechanism employed by viruses to evade the host's immune system. To date, studies have primarily evaluated molecular mimicry in the context of full protein structural mimics. However, recent work has demonstrated that short linear amino acid (AA) molecular mimics can elicit cross-reactive antibodies and T-cells from the host, which may contribute to development and progression of autoimmunity. Despite this, the prevalence of molecular mimics throughout the human virome has not been fully explored. In this study, we evaluate 134 human infecting viruses and find significant usage of linear mimicry across the virome, particularly those in the herpesviridae and poxviridae families. Furthermore, we identify that proteins involved in cellular replication and inflammation, those expressed from autosomes, the X chromosome, and in thymic cells are over-enriched in viral mimicry. Finally, we demonstrate that short linear mimicry from Epstein-Barr virus (EBV) is significantly higher in auto-antibodies found in multiple sclerosis patients to a greater degree than previously appreciated. Our results demonstrate that human-infecting viruses frequently leverage mimicry in the course of their infection, point to substantial evolutionary pressure for mimicry, and highlight mimicry's important role in human autoimmunity. Clinically, our findings could translate to development of novel therapeutic strategies that target viral infections linked to autoimmunity, with the goal of eliminating disease-associated latent viruses and preventing their reactivation.

Design of nanoparticle-based systems for the systemic delivery of chemotherapeutics: Alternative potential routes via sublingual and buccal administration for systemic drug delivery.

Conventional therapeutic approaches for cancer generally involve chemo- and radiation therapies that often exhibit low efficacy and induce toxic side effects. Recent years have seen significant advancements in the use of protein biologics as a promising alternative treatment option. Nanotechnology-based systems have shown great potential in providing more specific and targeted cancer treatments, thus improving upon many of the limitations associated with current treatments. The unique properties of biomaterial carriers at the nanoscale have been proven to enhance both the performance of the incorporated therapeutic agent and tumor targeting; however, many of these systems are delivered intravenously, which can cause hazardous side effects. Buccal and sublingual delivery systems offer an alternative route for more efficient delivery of nanotechnologies and drug absorption into systemic circulation. This review concentrates on emerging buccal and sublingual nanoparticle delivery systems for chemo- and protein therapeutics, their development, efficacy, and potential areas of improvement in the field. Several factors contribute to the development of effective buccal or sublingual nanoparticle delivery systems, including targeting efficiency of the nanoparticulate carriers, drug release, and carrier biocompatibility. Furthermore, the potential utilization of buccal and sublingual multilayer films combined with nanoparticle chemotherapeutic systems is outlined as a future avenue for in vitro and in vivo research.