The Effect of Epstein-Barr Virus Latent Membrane Protein 2 Expression on the Kinetics of Early B Cell Infection

Infection of human B cells with wild-type Epstein-Barr virus (EBV) in vitro leads to activation and proliferation that result in efficient production of lymphoblastoid cell lines (LCLs). Latent Membrane Protein 2 (LMP2) is expressed early after infection and previous research has suggested a possible role in this process. Therefore, we generated recombinant EBV with knockouts of either or both protein isoforms, LMP2A and LMP2B (Δ2A, Δ2B, Δ2A/Δ2B) to study the effect of LMP2 in early B cell infection. Infection of B cells with Δ2A and Δ2A/Δ2B viruses led to a marked decrease in activation and proliferation relative to wild-type (wt) viruses, and resulted in higher percentages of apoptotic B cells. Δ2B virus infection showed activation levels comparable to wt, but fewer numbers of proliferating B cells. Early B cell infection with wt, Δ2A and Δ2B viruses did not result in changes in latent gene expression, with the exception of elevated LMP2B transcript in Δ2A virus infection. Infection with Δ2A and Δ2B viruses did not affect viral latency, determined by changes in LMP1/Zebra expression following BCR stimulation. However, BCR stimulation of Δ2A/Δ2B cells resulted in decreased LMP1 expression, which suggests loss of stability in viral latency. Long-term outgrowth assays revealed that LMP2A, but not LMP2B, is critical for efficient long-term growth of B cells in vitro. The lowest levels of activation, proliferation, and LCL formation were observed when both isoforms were deleted. These results suggest that LMP2A appears to be critical for efficient activation, proliferation and survival of EBV-infected B cells at early times after infection, which impacts the efficient long-term growth of B cells in culture. In contrast, LMP2B did not appear to play a significant role in these processes, and long-term growth of infected B cells was not affected by the absence of this protein. © 2013 Wasil et al

Epstein-Barr virus: clinical and epidemiological revisits and genetic basis of oncogenesis

Epstein-Barr virus (EBV) is classified as a member in the order herpesvirales, family herpesviridae, subfamily gammaherpesvirinae and the genus lymphocytovirus. The virus is an exclusively human pathogen and thus also termed as human herpesvirus 4 (HHV4). It was the first oncogenic virus recognized and has been incriminated in the causation of tumors of both lymphatic and epithelial nature. It was reported in some previous studies that 95% of the population worldwide are serologically positive to the virus. Clinically, EBV primary infection is almost silent, persisting as a life-long asymptomatic latent infection in B cells although it may be responsible for a transient clinical syndrome called infectious mononucleosis. Following reactivation of the virus from latency due to immunocompromised status, EBV was found to be associated with several tumors. EBV linked to oncogenesis as detected in lymphoid tumors such as Burkitt's lymphoma (BL), Hodgkin's disease (HD), post-transplant lymphoproliferative disorders (PTLD) and T-cell lymphomas (e.g. Peripheral T-cell lymphomas; PTCL and Anaplastic large cell lymphomas; ALCL). It is also linked to epithelial tumors such as nasopharyngeal carcinoma (NPC), gastric carcinomas and oral hairy leukoplakia (OHL). In vitro, EBV many studies have demonstrated its ability to transform B cells into lymphoblastoid cell lines (LCLs). Despite these malignancies showing different clinical and epidemiological patterns when studied, genetic studies have suggested that these EBV- associated transformations were characterized generally by low level of virus gene expression with only the latent virus proteins (LVPs) upregulated in both tumors and LCLs. In this review, we summarize some clinical and epidemiological features of EBV- associated tumors. We also discuss how EBV latent genes may lead to oncogenesis in the different clinical malignancie

A Twin Study of ADHD Symptoms in Early Adolescence: Hyperactivity-impulsivity and Inattentiveness Show Substantial Genetic Overlap but Also Genetic Specificity

Item does not contain fulltextA previous paper in this journal revealed substantial genetic overlap between the ADHD dimensions of hyperactivity-impulsivity and inattentiveness in a sample of 8-year old twins drawn from a UK-representative population sample. Four years later, when the twins were 12 years old, more than 5,500 pairs drawn from the same sample were rated again on the DSM-IV based Revised Conners' Parent Rating Scale to assess symptoms on both ADHD dimensions. Heritabilities were high (around 70%) for both hyperactivity-impulsivity and inattentiveness and evidence for etiological sex differences was absent. The critical finding was a genetic correlation of 0.55, indicating that hyperactivity-impulsivity and inattentiveness are substantially influenced by the same genes but that the two dimensions also show large and significant unique genetic effects. These results in early adolescence confirm our findings in middle childhood, providing evidence for substantial genetic overlap as well as genetic heterogeneity of the ADHD dimensions. Future genetic studies should investigate the ADHD dimensions separately

Time resolved studies of interatomic Coulombic decay

Interatomic Coulombic decay (ICD) is a decay mechanism occurring in loosely bound matter, e.g. in systems bound by van der Waals-forces or hydrogen bonds. In many such cases the decay time is similar to the time scale of nuclear motion during the decay. As the efficiency of ICD strongly depends on the internuclear distance of the atoms or molecules involved in the decay, an overall non-trivial temporal decay behavior arises. The progress of examining the time-domain aspects of interatomic Coulombic decay is summarized in this short topical review with a special emphasis on experiments that are now feasible due to the developments of free-electron lasers

Few-femtosecond timing at fourth-generation X-ray light sources

The combined qualities of ultra high intensity and ultra short pulse duration, available at 4th generation X ray light sources provide tremendous opportunities for investigation of ultrafast dynamics in complex systems. Such studies require femtosecond synchronization between pump and probe laser pulses. However, the necessary level of stability of the accelerator is currently impossible to achieve. Fortunately, this issue can be managed if the relative timing jitter between light sources is accurately monitored, allowing subsequent data sorting. We present a new, robust, non invasive approach that provides 4.6 fs rms temporal resolution. This is, to our knowledge, the best resolution ever achieved between an FEL and an external laser. Our method employs coherent terahertz radiation generated at the end of the X ray undulator by the same electron bunch that emits the X ray pulse. Therefore, this method can be universally applied at any advanced light source working with ultra short electron bunches and undulator

Two-photon double ionization of Ne by free-electron laser radiation: a kinematically complete experiment

We present kinematically complete data on two-photon double ionization of Ne induced by short (∼25 fs) intense (∼5 × 1013 W cm−2) free-electron laser pulses at 44 eV. The observed electron energy spectrum points to the dominance of ‘sequential’ ionization. We analyse state-selective angular distributions as well as the two-electron angular correlation function, and suggest a method to determine the time delay between both ionization steps. The measured angular asymmetry ( ß-) parameters significantly deviate from the results of an earlier non-coincident experiment providing benchmark data for theory