The herpes simplex virus UL37 protein is phosphorylated in infected cells

The herpes simplex virus type 1 (HSV-1) UL37 open reading frame encodes a 120-kDa late ('yl), nonstructural protein in infected cells. Recent studies in our laboratory have demonstrated that the UL37 protein interacts in the cytoplasm of infected cells with ICP8, the major HSV-1 DNA-binding protein. As a result of this interaction, the UL37 protein is transported to the nucleus and can be coeluted with ICP8 from single-stranded DNA columns. Pulse-labeling and pulse-chase studies of HSV-1-infected cells with [35S]methionine and 32p; demonstrated that UL37 was a phosphoprotein which did not have a detectable rate of turnover. The protein was phosphorylated soon after translation and remained phosphorylated throughout the viral replicative cycle. U137 protein expressed from a vaccinia virus recombinant was also phosphorylated during infection, suggesting that the UL37 protein was phosphorylated by a cellular kinase and that interaction with the ICP8 protein was not a prerequisite for UL37 phosphorylation. Phosphorylation of proteins is an important posttranslational modification that has been shown to modulate a variety of macromolecular events, including transcription, translation, and viral transformation (14). Most transcription factors are phosphorylated The herpes simplex virus type 1 (HSV-1) genome is a linear, double-stranded DNA molecule of 160 kbp which encodes at least 75 separate proteins Workers in our laboratory have previously reported on the identification and characterization of the HSV-1 UL37 protein. The UL37 open reading frame, which is located in the unique long sequences of the viral DNA genome, encodes a nonstructural protein with an apparent molecular mass of 120 kDa In this article, we report that the UL37 protein was stably phosphorylated in HSV-1-infected cells. Phosphorylation of the UL37 protein did not require interaction with the ICP8 protein and was most likely the result of the action of a cellular kinase. The phosphorylation of the UL37 protein occurred soon after translation, and the phosphate did not appear to cycle on and off during viral replication. MATERIALS AND METHODS Cells and viruses. Vero cells (American Type Culture Collection) were grown in Eagle's minimal essential medium (EMEM) supplemented with 10% (vol/vol) Serum-Plus (JRH, Rockville, Md.) and 50 p.g of gentamicin (USB

Hyperfine Interactions in Charm and Bottom Systems

Hyperfine interactions in the light meson and baryon sectors are generalized to the charm and bottom systems. It is pointed out that an attempt to increase the value of the wave function at the origin to account for the unusual ratio of $\Lambda_{b}$ to the $B^0$ lifetimes could spoil the good agreement among the baryon and meson hyperfine mass-splitting. Including spin effects and taking phase space differences into account we predict that the decay rate of the $\Lambda_{b}$ can be increased relative to that of the $B^0$ meson by about 7%.Comment: 10 pages, plain Latex, no figures. A new isospin argument has been adde

Deprivation, Violence, and Identities: Mapping Contemporary World Conflicts

The University Archives has determined that this item is of continuing value to OSU's history.With the collapse of the Soviet Union, many anticipated the advent of a “new world order” of global capitalism, or even an “end to history,” implying that conflicts based on ideology and competing national interests and identities would lose their political relevance in the post-Cold War era. Quite to the contrary, the 1990s saw an upwelling of ethnic and religious violence in locations as disparate as the former Yugoslavia, Central Africa, South Asia, and the Middle East. Prior to the events of 9/11, the structure of international relations had still made it possible to imagine that such conflicts had local roots and were thus exclusively of regional consequence. The events of 9/11, however, rendered undeniable the global significance of local ethnic and religious-based differences. It is now an inescapable conclusion that social identities are everywhere threatened from within by local and ethnic formations, conditioned in their response by the prerogatives and ambitions of the state and its actors, and transformed from without by the global flows of capital, popular culture, and transnational ideologies and populations. As features of the contemporary world, deprivation, violence, and identities are but the local manifestations of the conflict between global systems of thought, power, and authority.Ohio State University. Center for African StudiesOhio State University. Office of International AffiarsOhio State University. East Asian Studies CenterOhio State University. Center for Slavic and East European StudiesOhio State University. Middle East Studies CenterOhio State University. Office of International Affairs. Clusters of Interdisciplinary Research on International Themes (CIRIT)Ohio State University. Center for Latin American StudiesOhio State University. Mershon Center for International Security StudiesEvent webpage, event summar

Massive perturbers and the efficient merger of binary massive black holes

We show that dynamical relaxation in the aftermath of a galactic merger and the ensuing formation and decay of a binary massive black hole (MBH), are dominated by massive perturbers (MPs) such as giant molecular clouds or clusters. MPs accelerate relaxation by orders of magnitude relative to 2-body stellar relaxation alone, and efficiently scatter stars into the binary MBH's orbit. The 3-body star-binary MBH interactions shrink the binary MBH to the point where energy losses from the emission of gravitational waves (GW) lead to rapid coalescence. We model this process based on observed and simulated MP distributions and take into account the decreased efficiency of the star-binary MBH interaction due to acceleration in the galactic potential. We show that mergers of gas-rich galactic nuclei lead to binary MBH coalescence well within the Hubble time. Moreover, lower-mass binary MBHs (<10^8 Msun) require only a few percent of the typical gas mass in a post-merger nucleus to coalesce in a Hubble time. The fate of a binary MBH in a gas poor galactic merger is less certain, although massive stellar structures (e.g. clusters, stellar rings) could likewise lead to efficient coalescence. These coalescence events are observable by their strong GW emission. MPs thus increase the cosmic rate of such GW events, lead to a higher mass deficit in the merged galactic core and suppress the formation of triple MBH systems and the resulting ejection of MBHs into intergalactic space.Comment: 14 pages, 4 figures, 3 tables. More detailed explanations and changes in structure. Section on hypervelocity stars moved to another paper (in preparation). Results and conclusions unchanged. Accepted to Ap

DELETION OF THE HERPES SIMPLEX VIRUS 1 INTERNAL REPEAT SEQUENCES AFFECTS PATHOGENICITY IN THE MOUSE

ABSTRACT We have isolated three different herpes simplex virus 1 (HSV-1) recombinant viruses, each frozen in either the P (prototype), IS (inversion of S component), or ILS (inversion of both components) genome arrangement. Common to all three recombinant viruses is the deletion of approximately 14 kilobases (kb) of viral DNA sequences representing greater than 95% of the internal repeat sequences and the insertion of a 9.6 kb mini-Mu genome containing a functional thymidine kinase gene. No unique DNA sequences were deleted from the viral genomes. Analyses of growth curves of the wild-type and recombinant viruses in cell culture has revealed that the recombinants grow somewhat more slowly, producing final titers within 1.5 logs of wild-type HSV-1(F). There is no discernible difference in plaque size or plaque morphology between the recombinant and wild type strains. Analysis of the recombinant viruses in mice reveals the following: I), the recombinant viruses are essentially avirulent, exhibiting drastically increased LD50 values as compared to the wild-type strain by intracerebral injection; ii), the recombinant viruses are not neuroinvasive in that they do not spread from the cornea to sensory ganglion; iii), the recombinant viruses exhibit minimal local replication both in the corneas of infected mice and in the brains of mice inoculated by intracerebral injection; and iv), the recombinant viruses do not establish a reactivable latent infection in the trigeminal ganglion following either intracerebral inoculation or inoculation of scarified corneas. These properties suggest a unique pattern of pathogenesis for HSV mutants in the mouse model

A case-cohort study of human herpesvirus 8 seropositivity and incident prostate cancer in Tobago

<p>Abstract</p> <p>Background</p> <p>We previously reported a cross-sectional association between the presence of human herpesvirus 8 (HHV-8) serum antibodies and screen-detected prostate cancer in men living in Tobago. In the same study population, we examined the association between HHV-8 seropositivity and incident prostate cancer discovered at later screenings.</p> <p>Methods</p> <p>In 40-81 year-old men without prostate cancer discovered at initial digital rectal examination (DRE) and prostate-specific antigen (PSA) screening, a case-cohort design measured the association between baseline HHV-8 seropositivity (modified immunofluorescence assay for antibodies against HHV-8 lytic antigens) and incident prostate cancer detected at DRE and PSA screenings three or five years later.</p> <p>Results</p> <p>Analyses included 486 unique individuals, 96 incident prostate cancer cases, and 415 randomly selected subjects representing an at-risk cohort. By design, the random sub-cohort contained 25 incident prostate cancer cases. In the sub-cohort, the frequency of HHV-8 seropositivity increased across age groupings (40-49 years: 3.5%, 50-59 years: 13.6%, and ≥ 60 years: 22.9%). HHV-8 seropositivity was higher in men with elevated (≥ 4.0 ng/mL) than men with non-elevated PSA at initial screening (30.4% <it>vs</it>. 9.9% seropositive; crude odds ratio (OR) 3.96, 95% confidence interval (CI) 1.53-10.2; age-adjusted OR 2.42, 95% CI 0.91-6.47). HHV-8 seropositivity did not increase incident prostate cancer risk (age-adjusted hazard ratio (HR) 0.88, 95% CI 0.46-1.69).</p> <p>Conclusions</p> <p>Case-cohort analysis did not identify association between HHV-8 seropositivity and incident prostate cancer. However, analyses uncovered possible association between HHV-8 and PSA (a marker of prostate inflammation). Co-occurrence of HHV-8 seropositivity and PSA elevation may explain cross-sectional association between HHV-8 and PSA screen-detected prostate cancer.</p

Synergistic induction of cancer-related immunosuppression by β2-adrenergic stress mediators and P38MAPK inflammatory pathway

Psychological stress has been implicated in promoting cancer recurrence and progression, but the magnitude of this effect and underlying mechanism remain unclear. In attempt to address this controversy, we have evaluated the impact of stress on molecular and cellular components of cancer Immune-surveillance and tested the hypothesis that the impact of stress in promoting tumor-associated immune suppression is context-dependent