Rapid Immunoassay for the Detection of Genital Herpes Infection

Objective: We evaluated a new affinity membrane strip test for the diagnosis of herpetic genital infections. Test strip results, which are available by immunoassay in 30 min without the need for special equipment, were compared with the results of viral culture

Evidence that spontaneous reactivation of herpes virus does not occur in mice

BACKGROUND: Some species, including humans and rabbits, exhibit periodic viral reactivation and shed infectious virus at the infected end organ. Mice may be an exception, because spontaneous shedding of infectious virus rarely, if ever, occurs. However, spontaneous molecular reactivation, i.e., the expression of a few viral genes and the synthesis of the viral glycoproteins coded for by these genes, has been reported. This finding has prompted the assumption that molecular reactivation is an indicator of reactivation and the production of infectious virus. The goal of this study was to differentiate between viral gene expression during latency and the episodic production of infectious virus in mice. RESULTS: Viral reactivation and infection were not seen in herpes simplex virus type 1 (HSV-1) latent ganglion graft recipient BALB/c scid or immunocompetent BALB/c mice, which survived the 65-day observation period with no evidence of viral infection although the immunocompetent mice developed cellular and humoral immunity to HSV-1. In contrast, BALB/c scid recipients of ganglia containing reactivating virus invariably developed a local and, subsequently, systemic viral infection and died within 14 days. Immunocompetent BALB/c mice that received ganglion grafts containing reactivating virus survived the infection and became immune to the virus. Trigeminal ganglia removed from scid and immunocompetent recipient graft sites 5, 14, and 28 days after transplantation contained latent virus and viable neurons. CONCLUSION: The results suggest that, within the limits of detection of the experiments, spontaneous episodic production of immunogenic viral antigens but not of infectious virus occurs in mouse neural ganglia during latency

CLONAL CHARACTER OF F1 HYBRID LYMPHOCYTE SUBSET RECOGNITION OF PARENTAL CELLS IN ONE-WAY MIXED LYMPHOCYTE CULTURES

Proliferation of F1 hybrid lymphocytes in mixed lymphocyte cultures is stimulated by mitomycin-blocked parental cells. The demonstration of this phenomenon using F1 hybrids derived from congenic lines of mice establishes that the stimulation is controlled by genes in or closely linked to the major histocompatibility locus chromosome region. In agreement with the finding that tumor-bearing mice have an increased capacity for primary alloantigen recognition, it was observed that the F1 hybrid response to parent was also augmented by tumor bearing. Chromosomal analysis of dividing cells in one-way mixed cultures confirms that F1 cells, and not the blocked parental cells, enter mitosis. Stimulation of F1 cells by a soluble mediator liberated by the parental cells was not observed and mitomycin blocking of parental cells seems to be a completely effective blocking agent ensuring that parental cells can not enter DNA synthesis. The specificity and clonal nature of F1 recognition of parent was demonstrated using a 5-bromodeoxyuridine-suicide procedure. Distinct clones of lymphocytes in F1 spleen cell populations seem to recognize one or the other parent, but not both, in such experiments. These observations and others in tumor systems suggest that most or all heterozygous organisms may possess potentially self-reactive clones of lymphocytes

Re-evaluating the role of natural killer cells in innate resistance to herpes simplex virus type 1

BACKGROUND: Interferon-γ acts to multiply the potency with which innate interferons (α/β) suppress herpes simplex virus type 1 (HSV-1) replication. Recent evidence suggests that this interaction is functionally relevant in host defense against HSV-1. However, it is not clear which WBCs of the innate immune system, if any, limit HSV-1 spread in an IFN-γ dependent manner. The current study was initiated to determine if natural killer (NK) cells provide innate resistance to HSV-1 infection, and if so to determine if this resistance is IFN-γ-dependent. RESULTS: Lymphocyte-deficient scid or rag2(-/- )mice were used to test four predictions of the central hypothesis, and thus determine if innate resistance to HSV-1 is dependent on 1. NK cell cytotoxicity, 2. NK cells, 3. WBCs, or 4. the IFN-activated transcription factor, Stat 1. Loss of NK cell cytotoxic function or depletion of NK cells had no effect on the progression of HSV-1 infection in scid mice. In contrast, viral spread and pathogenesis developed much more rapidly in scid mice depleted of WBCs. Likewise, loss of Stat 1 function profoundly impaired the innate resistance of rag2(-/- )mice to HSV-1. CONCLUSION: Lymphocyte-deficient mice possess a very tangible innate resistance to HSV-1 infection, but this resistance is not dependent upon NK cells

ICP0 antagonizes Stat 1-dependent repression of herpes simplex virus: implications for the regulation of viral latency

BACKGROUND: The herpes simplex virus type 1 (HSV-1) ICP0 protein is an E3 ubiquitin ligase, which is encoded within the HSV-1 latency-associated locus. When ICP0 is not synthesized, the HSV-1 genome is acutely susceptible to cellular repression. Reciprocally, when ICP0 is synthesized, viral replication is efficiently initiated from virions or latent HSV-1 genomes. The current study was initiated to determine if ICP0's putative role as a viral interferon (IFN) antagonist may be relevant to the process by which ICP0 influences the balance between productive replication versus cellular repression of HSV-1. RESULTS: Wild-type (ICP0(+)) strains of HSV-1 produced lethal infections in scid or rag2(-/- )mice. The replication of ICP0(- )null viruses was rapidly repressed by the innate host response of scid or rag2(-/- )mice, and the infected animals remained healthy for months. In contrast, rag2(-/- )mice that lacked the IFN-α/β receptor (rag2(-/- )ifnar(-/-)) or Stat 1 (rag2(-/- )stat1(-/-)) failed to repress ICP0(- )viral replication, resulting in uncontrolled viral spread and death. Thus, the replication of ICP0(- )viruses is potently repressed in vivo by an innate immune response that is dependent on the IFN-α/β receptor and the downstream transcription factor, Stat 1. CONCLUSION: ICP0's function as a viral IFN antagonist is necessary in vivo to prevent an innate, Stat 1-dependent host response from rapidly repressing productive HSV-1 replication. This antagonistic relationship between ICP0 and the host IFN response may be relevant in regulating whether the HSV-1 genome is expressed, or silenced, in virus-infected cells in vivo. These results may also be clinically relevant. IFN-sensitive ICP0(- )viruses are avirulent, establish long-term latent infections, and induce an adaptive immune response that is highly protective against lethal challenge with HSV-1. Therefore, ICP0(- )viruses appear to possess the desired safety and efficacy profile of a live vaccine against herpetic disease

The Einstein Cross: constraint on dark matter from stellar dynamics and gravitational lensing

[Abridged] We present two-dimensional line-of-sight stellar kinematics of the lens galaxy in the Einstein Cross, obtained with the GEMINI 8m telescope, using the GMOS integral-field spectrograph. The velocity map shows regular rotation up to ~100 km/s around the minor axis of the bulge, consistent with axisymmetry. The velocity dispersion map shows a weak gradient increasing towards a central (R<1") value of sigma_0=170+/-9 km/s. We deproject the observed surface brightness from HST imaging to obtain a realistic luminosity density of the lens galaxy, which in turn is used to build axisymmetric dynamical models that fit the observed kinematic maps. We also construct a gravitational lens model that accurately fits the positions and relative fluxes of the four quasar images. We find that the resulting luminous and total mass distribution are nearly identical around the Einstein radius R_E = 0.89", with a slope that is close to isothermal, but which becomes shallower towards the center if indeed mass follows light. The dynamical model fits to the observed kinematic maps result in a total mass-to-light ratio (M/L)_dyn=3.7+/-0.5 M_sun/L_sun,I (in the I-band). This is consistent with the Einstein mass M_E = 1.54 x 10^10 M_sun divided by the (projected) luminosity within R_E, which yields a total mass-to-light ratio of (M/L)_E=3.4 M_sun/L_sun,I, with an error of at most a few per cent. We estimate from stellar populations model fits to colors of the lens galaxy a stellar mass-to-light ratio (M/L)_* from 2.8 to 4.1 M_sun/L_sun,I. Although a constant dark matter fraction of 20 per cent is not excluded, dark matter may play no significant role in the bulge of this ~L* early-type spiral galaxy.Comment: 18 pages, 8 figures, published in ApJ, 2010, 719, 148

Increasing condom use in heterosexual men: development of a theory-based interactive digital intervention

Increasing condom use to prevent sexually transmitted infections is a key public health goal. Interventions are more likely to be effective if they are theory- and evidence-based. The Behaviour Change Wheel (BCW) provides a framework for intervention development. To provide an example of how the BCW was used to develop an intervention to increase condom use in heterosexual men (the MenSS website), the steps of the BCW intervention development process were followed, incorporating evidence from the research literature and views of experts and the target population. Capability (e.g. knowledge) and motivation (e.g. beliefs about pleasure) were identified as important targets of the intervention. We devised ways to address each intervention target, including selecting interactive features and behaviour change techniques. The BCW provides a useful framework for integrating sources of evidence to inform intervention content and deciding which influences on behaviour to target

Massive black hole seeds from low angular momentum material

(ABRIDGED) We present a model in which the seeds of supermassive black holes form from the lowest angular momentum gas in proto-galaxies at high redshift. We show that this leads to a correlation between black hole masses and spheroid properties, as observed today. We assume that gas in early-forming, rare halos has a distribution of specific angular momentum similar to that expected for dark matter halos. This distribution has a significant low angular momentum tail which implies that every proto-galaxy should contain gas that ends up in a high-density disc. In halos more massive than a critical threshold of \~10^8Msun, the discs are gravitationally unstable, and experience an efficient Lin-Pringle viscosity that allows mass inflow. This process continues until the first massive stars disrupt the disc. Black holes are created with a characteristic mass of ~10^5 Msun, independent of the redshift of formation. This serves as a lower bound for black-hole masses in galaxies today. The comoving mass density of black hole seeds grows with time, and saturates when cosmic reionization stops gas cooling in these low-mass systems. By z~15, the comoving mass density becomes comparable to that inferred from observations, with room for appropriate additional luminous growth during a later quasar accretion phase. Hierarchical merging after z~15 naturally leads to a linear correlation between black-hole mass and stellar spheroid mass, with negligible black hole masses in disc-dominated galaxies.Comment: Replaced to match version accepted for publication in Mon. Not. R. Astron. So

A Census of Baryons and Dark Matter in an Isolated, Milky Way-sized Elliptical Galaxy

We present a study of the dark and luminous matter in the isolated elliptical galaxy NGC720, based on deep X-ray observations made with Chandra and Suzaku. The gas is reliably measured to ~R2500, allowing us to place good constraints on the enclosed mass and baryon fraction (fb) within this radius (M2500=1.6e12+/-0.2e12 Msun, fb(2500)=0.10+/-0.01; systematic errors are <~20%). The data indicate that the hot gas is close to hydrostatic, which is supported by good agreement with a kinematical analysis of the dwarf satellite galaxies. We confirm a dark matter (DM) halo at ~20-sigma. Assuming an NFW DM profile, our physical model for the gas distribution enables us to obtain meaningful constraints at scales larger than R2500, revealing that most of the baryons are in the hot gas. We find that fb within Rvir is consistent with the Cosmological value, confirming theoretical predictions that a ~Milky Way-mass (Mvir=3.1e12+/-0.4e12 Msun) galaxy can sustain a massive, quasi-hydrostatic gas halo. While fb is higher than the cold baryon fraction typically measured in similar-mass spiral galaxies, both the gas fraction (fg) and fb in NGC720 are consistent with an extrapolation of the trends with mass seen in massive galaxy groups and clusters. After correcting for fg, the entropy profile is close to the self-similar prediction of gravitational structure formation simulations, as observed in galaxy clusters. Finally, we find a strong heavy metal abundance gradient in the ISM similar to those observed in massive galaxy groups.Comment: 23 pages, 13 figures, 4 tables. Accepted for publication in the Astrophysical Journal. Minor modifications to match accepted version. Conclusions unchange