Manipulation of the host cell membrane by humanγ-herpesviruses EBV and KSHV for pathogenesis

The cell membrane regulates many physiological processes including cellular communication,homing and metabolism. It is therefore not surprising that the composition of the host cell membrane is manipulated by intracellular pathogens. Among these, the human oncogenic herpesviruses Epstein–Barr virus(EBV) and Kaposi's sarcoma-associated herpesvirus(KSHV)exploit the host cell membrane to avoid immune surveillance and promote viral replication.Accumulating evidence has shown that both EBV and KSHV directly encode several similar membrane-associated proteins, including receptors and receptor-specific ligands(cytokines and chemokines), to increase virus fitness in spite of host antiviral immune responses. These proteins are expressed individually at different phases of the EBV/KSHV life cycle and employ various mechanisms to manipulate the host cell membrane. In recent decades, much effort has been made to address how these membrane-based signals contribute to viral tumorigenesis. In this review, we summarize and highlight the recent understanding of how EBV and KSHV similarly manipulate host cell membrane signals, particularly how remodeling of the cell membrane allows EBV and KSHV to avoid host antiviral immune responses and favors their latent and lytic infection.

Can we treat neurodegenerative diseases by preventing an age-related decline in microRNA expression?

MicroRNA pathway is down-regulated in aged dopaminergic neurons： Parkinson＇s disease （PD） is the most frequent motor neuro- degenerative disorder and is morphologically mainly associated with progressive dopaminergic neuronal loss in the ventral midbrain.

Establishment of Novel Monoclonal Fabs Specific for Epstein-Barr Virus Encoded Latent Membrane Protein 1

Dear Editor,Epstein-Barr virus(EBV,also termed human herpesvirus-4)was the first identified human tumor virus.Since its discovery in 1964,studies have shown that EBV infects over 90%of all people by the time they are adults(Williams and Crawford 2006).EBV infection can result in mucocutaneous and systemic diseases,ranging from selflimited illnesses to aggressive malignancies,including B cell Hodgkin lymphoma and nasopharyngeal carcinoma.In vitro,EBV transforms resting B cells into proliferating blast cells(Pope et al.1968).

The complex role of PD-L1 in antitumor immunity:a recent update

PD-1,a member of the immunoglobulin gene superfamily,was found to be involved in programmed cell death and subsequently demonstrated to be critical for the negative regulation of T cells.Its ligands PD-L1(B7-H1)and PD-L2(B7-DC)interact with PD-1 and negatively regulate T cell-mediated immune responses.1 CD80 also interacts with PD-L1 as a counterreceptor.

Type I interferon： the mediator of bacterial infection-induced necroptosis

COMMENTARY Innate immune responses are essential for the host to fight against invading microbes. Innate immune receptors or pattern recog- nition receptors recognize conserved microbial molecules and trigger innate immune res- ponses. Pattern recognition receptors such as Toll-like receptors primarily signal through the adaptor MyD88 to activate NF-~B, while other Toll-like receptors signal v/a TRIF to activate IRF-3 resulting in the expression of type I interferons （IFNs）.a Type I IFNs play a crucial role in antiviral immune responses but are also important for the host response against bac- terial infection.2 Paradoxically.

The regulatory role of protein phosphorylation in human gammaherpesvirus associated cancers

Activation of specific sets of protein kinases by intracellular signal molecules has become more and more apparent in the past decade. Phosphorylation, one of key posttranslational modification events, is activated by kinase or regulatory protein and is vital for controlling many physiological functions of eukaryotic cells such as cell proliferation, differentiation, malignant transformation,and signal transduction mediated by external stimuli. Moreovers, the reversible modification of phosphorylation and dephosphorylation can result in different features of the target substrate molecules including DNA binding, protein-protein interaction, subcellular location and enzymatic activity, and is often hijacked by viral infection. Epstein-Barr virus(EBV) and Kaposi's sarcomaassociated herpesvirus(KSHV), two human oncogenic gamma-herpesviruses, are shown to tightly associate with many malignancies. In this review, we summarize the recent progresses on understanding of molecular properties and regulatory modes of cellular and viral proteins phosphorylation influenced by these two tumor viruses, and highlight the potential therapeutic targets and strategies against their related cancers.

：CL5 as a potential immunotherapeutic target in triple-negative breast cancer

Breast cancer （BC） is a leading cause of mortality among women in the world. To date, a number of molecules have been established as disease status indicators and therapeutic targets. The best known among them are estrogen receptor-α （ER-α）, progesterone receptor （PR） and H ER-2/neu. About 15%-20% BC patients do not respond effectively to thera pies targeting these classes of tumor-promoting factors. Thus, additional targets are strongly and urgently sought after in therapy for human BCs negative for ER, PR and HER-2, the so-called triple-negative BC （TNBC）. Recent clinical work has revealed that CC chemokine ligand 5 （CCL5） is strongly associated with the progression of BC, particularly TNBC. How CCL5 contributes to the development of TN BC is not well understood. Experimental animal studies have begun to address the mechanistic issue. In this article, we will review the clinical and laboratory work in this area that has led to our own hypothesis that targeting CCL5 in TNBCs will have favorable therapeutic outcomes with minimal adverse impact on the general physiology.