ABSTRACT
Transmission network analysis is a crucial evaluation tool aiming to explore the characteristics of the human immunodeficiency virus epidemic, develop evidence-based prevention strategies, and contribute to various areas of human immunodeficiency virus/acquired immunodeficiency syndrome prevention and control. Over recent decades, transmission networks have made tremendous strides in terms of modes, methods, applications, and various other aspects. Transmission network methods, including social, sexual, and molecular transmission networks, have played a pivotal role. Each transmission network research method has its advantages, as well as its limitations. In this study, we established a systematic review of these aforementioned transmission networks with respect to their definitions, applications, limitations, recent progress, and synthetic applications.
Subject(s)
Humans , Acquired Immunodeficiency Syndrome , Epidemics , HIV Infections/epidemiology , Sexual BehaviorABSTRACT
Ebola virus (EBOV) harbors an RNA genome encapsidated by nucleoprotein (NP) along with other viral proteins to form a nucleocapsid complex. Previous Cryo-eletron tomography and biochemical studies have shown the helical structure of EBOV nucleocapsid at nanometer resolution and the first 450 amino-acid of NP (NPΔ451-739) alone is capable of forming a helical nucleocapsid-like complex (NLC). However, the structural basis for NP-NP interaction and the dynamic procedure of the nucleocapsid assembly is yet poorly understood. In this work, we, by using an E. coli expression system, captured a series of images of NPΔ451-739 conformers at different stages of NLC assembly by negative-stain electron microscopy, which allowed us to picture the dynamic procedure of EBOV nucleocapsid assembly. Along with further biochemical studies, we showed the assembly of NLC is salt-sensitive, and also established an indispensible role of RNA in this process. We propose the diverse modes of NLC elongation might be the key determinants shaping the plasticity of EBOV virions. Our findings provide a new model for characterizing the self-oligomerization of viral nucleoproteins and studying the dynamic assembly process of viral nucleocapsid in vitro.
Subject(s)
Ebolavirus , Chemistry , Genetics , Metabolism , Escherichia coli , Genetics , Metabolism , Gene Expression , Nucleocapsid , Chemistry , Genetics , Metabolism , RNA, Viral , Chemistry , Genetics , Metabolism , Recombinant Proteins , Chemistry , Genetics , Metabolism , Virus AssemblyABSTRACT
Ebola virus (EBOV) causes hemorrhagic fever, resulting in mortality rates as high as 90% among infected humans and non-human primates (NHPs). The 2014 Ebola epidemic in West Africa is the severest in history, leading to WHO taking all control measures to stop any possibility of cross-border outbreaks. Because no licensed vaccines or effective therapeutics against EBOV are available, the current outbreak management has been limited to palliative care and barrier methods to prevent transmission. Several promising experimental EBOV vaccines have demonstrated protection in NHPs against lethal EBOV challenge, and some progresses have been made through clinical trials of EBOV vaccine candidates. It is believed there will be some licensed vaccine available in the near future to control EBOV outbreaks. In this review we provide some insights for further development of EBOV vaccines.
Subject(s)
Animals , Humans , Ebola Vaccines , Ebolavirus , Hemorrhagic Fever, EbolaABSTRACT
As the first line of immune defense for Mycobacterium tuberculosis (Mtb), macrophages also provide a major habitat for Mtb to reside in the host for years. The battles between Mtb and macrophages have been constant since ancient times. Triggered upon Mtb infection, multiple cellular pathways in macrophages are activated to initiate a tailored immune response toward the invading pathogen and regulate the cellular fates of the host as well. Toll-like receptors (TLRs) expressed on macrophages can recognize pathogen-associated-molecular patterns (PAMPs) on Mtb and mediate the production of immune-regulatory cytokines such as tumor necrosis factor (TNF) and type I Interferons (IFNs). In addition, Vitamin D receptor (VDR) and Vitamin D-1-hydroxylase are up-regulated in Mtb-infected macrophages, by which Vitamin D participates in innate immune responses. The signaling pathways that involve TNF, type I IFNs and Vitamin D are inter-connected, which play critical roles in the regulation of necroptosis, apoptosis, and autophagy of the infected macrophages. This review article summarizes current knowledge about the interactions between Mtb and macrophages, focusing on cellular fates of the Mtb-infected macrophages and the regulatory molecules and cellular pathways involved in those processes.
Subject(s)
Animals , Humans , Apoptosis , Autophagy , Interferon Type I , Metabolism , Macrophages , Allergy and Immunology , Metabolism , Mycobacterium tuberculosis , Physiology , Receptors, Calcitriol , Metabolism , Steroid Hydroxylases , Metabolism , Toll-Like Receptors , Metabolism , Tuberculosis , Allergy and Immunology , Metabolism , Pathology , Tumor Necrosis Factors , MetabolismABSTRACT
LZ-8 protein, isolated from a well known Chinese traditional medicinal fungus Ganoderma lucidum, is the first member of fungal immunomodulatory protein, members of which have been isolated from a variety of medicinal and edible mushrooms in the last two decades. The protein plays a multifunctional and important role in modulating immune system. In this report, in order to get LZ-8 protein crystals, the LZ-8 gene was expressed and purified by affinity chromatography, gel filtration chromatography and anion exchange chromatography subsequently. The protein was then crystallized using the hanging-drop vapour-diffusion method. The LZ-8 crystals were obtained and the phase information was calculated by X-ray diffraction. The resolution of LZ-8 crystals is 3.2A. This study will provide an insight into the structure of fungal immunomodulatory proteins.