肿瘤坏死因子受体超家族成员死亡受体在病毒感染中的作用

死亡受体是一组具有死亡结构域的膜受体，属于肿瘤坏死因子受体超家族成员。表达死亡受体的细胞与其相应的配体结合后可引发细胞凋亡，因此死亡受体参与机体的多种生理和病理过程，特别是在多种病毒感染中发挥着双重作用。本就最新发现的死亡受体在肝炎病毒、HIV以及巨细胞病毒等多种病毒感染中的作用作一综述。     

乙肝病毒感染相关受体的研究现状

乙肝病毒与细胞受体的结合是病毒感染宿主细胞的第一步,它决定病毒能否成功感染细胞,因此阻断HBV与其受体的结合是治疗乙型肝炎的重要途径之一.迄今为止,虽然有很多HBV感染可能起作用的受体的研究报道,但至今仍无法确定到底是什么受体或什么中介分子起关键作用.本文就与乙肝病毒感染相关的受体研究现状作一综述.     

乙肝病毒感染相关受体的研究现状

乙肝病毒与细胞受体的结合是病毒感染宿主细胞的第一步,它决定病毒能否成功感染细胞,因此阻断HBV与其受体的结合是治疗乙型肝炎的重要途径之一.迄今为止,虽然有很多HBV感染可能起作用的受体的研究报道,但至今仍无法确定到底是什么受体或什么中介分子起关键作用.本文就与乙肝病毒感染相关的受体研究现状作一综述.     

乙肝病毒感染相关受体的研究现状

乙肝病毒与细胞受体的结合是病毒感染宿主细胞的第一步,它决定病毒能否成功感染细胞,因此阻断HBV与其受体的结合是治疗乙型肝炎的重要途径之一.迄今为止,虽然有很多HBV感染可能起作用的受体的研究报道,但至今仍无法确定到底是什么受体或什么中介分子起关键作用.本文就与乙肝病毒感染相关的受体研究现状作一综述.     

乙肝病毒感染相关受体的研究现状

乙肝病毒与细胞受体的结合是病毒感染宿主细胞的第一步,它决定病毒能否成功感染细胞,因此阻断HBV与其受体的结合是治疗乙型肝炎的重要途径之一.迄今为止,虽然有很多HBV感染可能起作用的受体的研究报道,但至今仍无法确定到底是什么受体或什么中介分子起关键作用.本文就与乙肝病毒感染相关的受体研究现状作一综述.     

乙肝病毒感染相关受体的研究现状

乙肝病毒与细胞受体的结合是病毒感染宿主细胞的第一步,它决定病毒能否成功感染细胞,因此阻断HBV与其受体的结合是治疗乙型肝炎的重要途径之一.迄今为止,虽然有很多HBV感染可能起作用的受体的研究报道,但至今仍无法确定到底是什么受体或什么中介分子起关键作用.本文就与乙肝病毒感染相关的受体研究现状作一综述.     

乙肝病毒感染相关受体的研究现状

乙肝病毒与细胞受体的结合是病毒感染宿主细胞的第一步,它决定病毒能否成功感染细胞,因此阻断HBV与其受体的结合是治疗乙型肝炎的重要途径之一.迄今为止,虽然有很多HBV感染可能起作用的受体的研究报道,但至今仍无法确定到底是什么受体或什么中介分子起关键作用.本文就与乙肝病毒感染相关的受体研究现状作一综述.     

乙肝病毒感染相关受体的研究现状

乙肝病毒与细胞受体的结合是病毒感染宿主细胞的第一步,它决定病毒能否成功感染细胞,因此阻断HBV与其受体的结合是治疗乙型肝炎的重要途径之一.迄今为止,虽然有很多HBV感染可能起作用的受体的研究报道,但至今仍无法确定到底是什么受体或什么中介分子起关键作用.本文就与乙肝病毒感染相关的受体研究现状作一综述.     

乙肝病毒感染相关受体的研究现状

乙肝病毒与细胞受体的结合是病毒感染宿主细胞的第一步,它决定病毒能否成功感染细胞,因此阻断HBV与其受体的结合是治疗乙型肝炎的重要途径之一.迄今为止,虽然有很多HBV感染可能起作用的受体的研究报道,但至今仍无法确定到底是什么受体或什么中介分子起关键作用.本文就与乙肝病毒感染相关的受体研究现状作一综述.     

乙肝病毒感染相关受体的研究现状

乙肝病毒与细胞受体的结合是病毒感染宿主细胞的第一步,它决定病毒能否成功感染细胞,因此阻断HBV与其受体的结合是治疗乙型肝炎的重要途径之一.迄今为止,虽然有很多HBV感染可能起作用的受体的研究报道,但至今仍无法确定到底是什么受体或什么中介分子起关键作用.本文就与乙肝病毒感染相关的受体研究现状作一综述.     

Sphingosine kinase 1 in viral infections

Sphingosine kinase 1 (SphK1) is an enzyme that phosphorylates the lipid sphingosine to generate sphingosine‐1‐phosphate (S1P). S1P can act intracellularly as a signaling molecule and extracellularly as a receptor ligand. The SphK1/S1P axis has well‐described roles in cell signaling, the cell death/survival decision, the production of a pro‐inflammatory response, immunomodulation, and control of vascular integrity. Agents targeting the SphK1/S1P axis are being actively developed as therapeutics for cancer and immunological and inflammatory disorders. Control of cell death/survival and pro‐inflammatory immune responses is central to the pathology of infectious disease, and we can capitalize on the knowledge provided by investigations of SphK1/S1P in cancer and immunology to assess its application to selected human infections. We have herein reviewed the growing literature relating viral infections to changes in SphK1 and S1P. SphK1 activity is reportedly increased following human cytomegalovirus and respiratory syncytial virus infections, and elevated SphK1 enhances influenza virus infection. In contrast, SphK1 activity is reduced in bovine viral diarrhea virus and dengue virus infections. Sphingosine analogs that modulate S1P receptors have proven useful in animal models in alleviating influenza virus infection but have shown no benefit in simian human immunodeficiency virus and lymphocytic choriomeningitis virus infections. We have rationalized a role for SphK1/S1P in dengue virus, chikungunya virus, and Ross River virus infections, on the basis of the biology and the pathology of these diseases. The increasing number of effective SphK1 and S1P modulating agents currently in development makes it timely to investigate these roles with the potential for developing modulators of SphK1 and S1P for novel anti‐viral therapies. Copyright © 2012 John Wiley & Sons, Ltd.     

Insights into the interaction between influenza virus and pneumococcus

Bacterial infections following influenza are an important cause of morbidity and mortality worldwide. Based on the historical importance of pneumonia as a cause of death during pandemic influenza, the increasingly likely possibility that highly pathogenic avian influenza viruses will trigger the next worldwide pandemic underscores the need to understand the multiple mechanisms underlying the interaction between influenza virus and bacterial pathogens such as Streptococcus pneumoniae. There is ample evidence to support the historical view that influenza virus alters the lungs in a way that predisposes to adherence, invasion, and induction of disease by pneumococcus. Access to receptors is a key factor and may be facilitated by the virus through epithelial damage, by exposure or up-regulation of receptors, or by provoking the epithelial regeneration response to cytotoxic damage. More recent data indicate that alteration of the immune response by diminishing the ability of the host to clear pneumococcus or by amplification of the inflammatory cascade is another key factor. Identification and exploration of the underlying mechanisms responsible for this synergism will provide targets for prevention and treatment using drugs and vaccines.     

Opportunistic infections in adults with acquired immunodeficiency syndrome: a comparison of clinical and autopsy findings.

BACKGROUND AND PURPOSE: Many opportunistic infections causing death in acquired immunodeficiency syndrome (AIDS) patients are often not diagnosed prior to death. The objective of this study was to compare the premortem and postmortem diagnoses of opportunistic infections and tumors among 15 AIDS patients treated in a hospital in southern Taiwan. METHODS: Total autopsy (brain, chest and abdominal cavity) was performed in 2 patients, and partial autopsy in 13. RESULTS: Pneumocystis carinii pneumonia, candidiasis, lymphoma, Kaposi's sarcoma, toxoplasmosis and salmonellosis were more commonly diagnosed before death than at autopsy. By contrast, cytomegalovirus (CMV) infections and herpes simplex virus or varicella-zoster virus infections were more frequently diagnosed at postmortem examinations than prior to death. CONCLUSIONS: In conclusion, this study found substantial discrepancies between autopsy findings and premortem clinical diagnoses in AIDS patients, especially for CMV infection.     

Herpes simplex virus and toll-like receptors

The earliest interactions between viruses and host cells are critical to determining the outcome of infections. The interactions between a virus and its host cells that lead to the production of inflammatory cytokines are essential to the development of T cells and antibodies that provide long-term defense against the invaders. At the same time, however, these same cytokines (or sometimes other mediators or chemokines) stimulate inflammation, which may lead to localized tissue damage and/or systemic circulatory collapse and death. This review focuses on the interaction between Toll-like receptors, a critical component of the innate immune system of mammals, and their role in herpes simplex pathogenesis and immunity.     

Virus infections in bone marrow transplant recipients: a three year prospective study.

Over three years 81 consecutive bone marrow transplant recipients (32 allogeneic and 49 autologous) who received prophylaxis with acyclovir, were studied for symptomatic virus infection. Thirty nine infections were documented in a total of 28 patients. Thirty two infections were mild, five were moderately severe, and two were severe. Cytomegalovirus infection occurred in only six allogeneic recipients. Herpes simplex virus and varicella zoster virus infections occurred infrequently. Seven patients who were considered at the time of death to have died due to an infectious cause were studied virologically at necropsy. In only one patient was a virus infection thought to have been the cause of death. Prophylaxis with acyclovir may have influenced the rate and clinical prominence of herpes virus infections. In this study viruses were considered to have had a relatively minor role in causing morbidity and mortality.     

TLRs/NLRs: Shaping the landscape of host immunity

Innate immune system provides the first line of defense against pathogenic organisms. It has a varied and large collection of molecules known as pattern recognition receptors (PRRs) which can tackle the pathogens promptly and effectively. Toll-like receptors (TLRs) and NOD-like receptors (NLRs) are members of the PRR family that recognize pathogen associated molecular patterns (PAMPs) and play pivotal roles to mediate defense against infections from bacteria, fungi, virus and various other pathogens. In this review, we discuss the critical roles of TLRs and NLRs in the regulation of host immune-effector functions such as cytokine production, phagosome-lysosome fusion, inflammasome activation, autophagy, antigen presentation, and B and T cell immune responses that are known to be essential for mounting a protective immune response against the pathogens. This review may be helpful to design TLRs/NLRs based immunotherapeutics to control various infections and pathophysiological disorders.     

MDA5/RIG-I and virus recognition

The innate immune system initially recognizes RNA virus infection and evokes antiviral responses by producing type I interferons (IFNs). Toll-like receptors (TLRs) and cytoplasmic retinoic acid-inducible gene I (RIG-I)-like helicases (RLHs) are the two major receptor systems for detecting RNA viruses. The RLH signaling pathways play essential roles in the recognition of RNA viruses in various cells, with the exception of plasmacytoid dendritic cells, which utilize TLRs for virus recognition. The route of infection determines the cell types responsible for type I IFN production. Recent studies have suggested that TLRs are critical for activation of adaptive immune responses against several virus infections, although it may be premature to draw such a conclusion for virus infections in general. In this review, we will discuss recent advances toward clarifying the signaling pathways activated by RLHs and TLRs.     

Clinical potential of DAS181 for treatment of parainfluenza-3 infections in transplant recipients

Parainfluenza virus (PIV) infections can cause serious respiratory infections and death in immunocompromised patients. No antiviral agents have proven efficacy against PIV, and therapy generally consists of supportive care. DAS181, a novel sialidase fusion protein that temporarily disables airway epithelial PIV receptors by enzymatic removal of sialic acid moieties, has been shown to inhibit infection with PIV strains in vitro and in an animal model. We describe here the clinical course of 2 immunocompromised patients with PIV-3 infection, one with a history of lung transplantation and the other neutropenic after autologous hematopoietic stem cell transplantation for multiple myeloma. Both patients had substantial clinical improvement in respiratory and systemic symptoms after a 5-day DAS181 treatment course, although the clinical improvement in the autologous stem cell transplantation patient also paralleled neutrophil engraftment.     

Etiology of acute viral respiratory infections common in Pakistan: A review

Respiratory infections, especially those of the lower respiratory tract, remain a foremost cause of mortality and morbidity of children greater than 5 years in developing countries including Pakistan. Ignoring these acute‐level infections may lead to complications. Particularly in Pakistan, respiratory infections account for 20% to 30% of all deaths of children. Even though these infections are common, insufficiency of accessible data hinders development of a comprehensive summary of the problem. The purpose of this study was to determine the prevalence rate in various regions of Pakistan and also to recognize the existing viral strains responsible for viral respiratory infections through published data. Respiratory viruses are detected more frequently among rural dwellers in Pakistan. Lower tract infections are found to be more lethal. The associated pathogens comprise respiratory syncytial virus (RSV), human metapneumovirus (HMPV), coronavirus, enterovirus/rhinovirus, influenza virus, parainfluenza virus, adenovirus, and human bocavirus. RSV is more dominant and can be subtyped as RSV‐A and RSV‐B (BA‐9, BA‐10, and BA‐13). Influenza A (H1N1, H5N1, H3N2, and H1N1pdm09) and Influenza B are common among the Pakistani population. Generally, these strains are detected in a seasonal pattern with a high incidence during spring and winter time. The data presented include pneumonia, bronchiolitis, and influenza. This paper aims to emphasise the need for standard methods to record the incidence and etiology of associated pathogens in order to provide effective treatment against viral infections of the respiratory tract and to reduce death rates.