ISGRI: the INTEGRAL Soft Gamma-Ray Imager

For the first time in the history of high energy astronomy, a large CdTe gamma-ray camera is operating in space. ISGRI is the low-energy camera of the IBIS telescope on board the INTEGRAL satellite. This paper details its design and its in-flight behavior and performances. Having a sensitive area of 2621 cm$^2$ with a spatial resolution of 4.6 mm, a low threshold around 12 keV and an energy resolution of $\sim$ 8% at 60 keV, ISGRI shows absolutely no signs of degradation after 9 months in orbit. All aspects of its in-flight behavior and scientific performance are fully nominal, and in particular the observed background level confirms the expected sensitivity of 1 milliCrab for a 10$^6$s observation.Comment: INTEGRAL A&A special issu

Gene therapy: the end of the rainbow?

The increased understanding of the molecular basis of oral cancer has led to expectations that correction of the genetic defects will lead to improved treatments. Nevertheless, the first clinical trials for gene therapy of oral cancer occurred 20 years ago, and routine treatment is still not available. The major difficulty is that genes are usually delivered by virus vectors whose effects are weak and temporary. Viruses that replicate would be better, and the field includes many approaches in that direction. If any of these are effective in patients, then gene therapy will become available in the next few years. Without significant advances, however, the treatment of oral cancer by gene therapy will remain as remote as the legendary pot of gold at the end of the rainbow

A Live-Attenuated HSV-2 ICP0− Virus Elicits 10 to 100 Times Greater Protection against Genital Herpes than a Glycoprotein D Subunit Vaccine

Glycoprotein D (gD-2) is the entry receptor of herpes simplex virus 2 (HSV-2), and is the immunogen in the pharmaceutical industry's lead HSV-2 vaccine candidate. Efforts to prevent genital herpes using gD-2 subunit vaccines have been ongoing for 20 years at a cost in excess of $100 million. To date, gD-2 vaccines have yielded equivocal protection in clinical trials. Therefore, using a small animal model, we sought to determine if a live-attenuated HSV-2 ICP0− virus would elicit better protection against genital herpes than a gD-2 subunit vaccine. Mice immunized with gD-2 and a potent adjuvant (alum+monophosphoryl lipid A) produced high titers of gD-2 antibody. While gD-2-immunized mice possessed significant resistance to HSV-2, only 3 of 45 gD-2-immunized mice survived an overwhelming challenge of the vagina or eyes with wild-type HSV-2 (MS strain). In contrast, 114 of 115 mice immunized with a live HSV-2 ICP0− virus, 0ΔNLS, survived the same HSV-2 MS challenges. Likewise, 0ΔNLS-immunized mice shed an average 125-fold less HSV-2 MS challenge virus per vagina relative to gD-2-immunized mice. In vivo imaging demonstrated that a luciferase-expressing HSV-2 challenge virus failed to establish a detectable infection in 0ΔNLS-immunized mice, whereas the same virus readily infected naïve and gD-2-immunized mice. Collectively, these results suggest that a HSV-2 vaccine might be more likely to prevent genital herpes if it contained a live-attenuated HSV-2 virus rather than a single HSV-2 protein

Colonization of murine ganglia by a superinfecting strain of herpes simplex virus

We report on the colonization of murine trigeminal ganglia after sequential infection of mice by herpes simplex viruses (HSVs). In preliminary studies, we have established that whereas the HSV-1(F) strain efficiently colonizes ganglia when inoculated by either the ear or eye routes, the HSV-1 X HSV-2 recombinant C7D colonizes ganglia when inoculated by the eye route only. The experimental design consisted of inoculating the right eye with C7D on day 1 and with HSV-1(F) in both left and right eyes on day 26. Both right and left trigeminal ganglia were removed and analyzed independently for latent virus on day 52. Our studies indicate that HSV-1(F) viruses were recovered from all left trigeminal ganglia but from only a small number of right trigeminal ganglia. Some right trigeminal ganglia yielded no viruses, whereas others yielded both C7D and HSV-1(F) viruses identified on the basis of plaque morphology and restriction enzyme cleavage patterns of viral DNA. The results indicate that more than one virus may colonize the same ganglion and that trigeminal ganglia may be protected from colonization by a superinfecting virus by determinants acting at a local level in the absence of demonstrable virus.</jats:p

Establishment of latency in mice by herpes simplex virus 1 recombinants that carry insertions affecting regulation of the thymidine kinase gene

Herpes simplex virus 1 recombinants carrying alpha-, beta-, and late gamma (gamma 2)-regulated thymidine kinase (TK) genes were tested for the ability to establish latency in BALB/c mice inoculated by the eye route. The significant findings were as follows. Representatives of alpha- and gamma 2-regulated TK recombinants all established and maintained latent infections, but the efficiency was somewhat lower than that of wild-type virus. Of the three alpha TK recombinants tested, one (R316) spontaneously deleted portions of the inserted sequences which conferred alpha regulation to the TK gene. The viruses carrying these deletions expressed considerably lower TK activity than did wild-type virus, i.e., 2 to 40% of the levels expressed by the wild-type virus carrying the beta TK gene. However, the ability of these viruses to establish latency was not related to the efficiency of expression of the TK gene. These results indicate the following: (i) conversion of the TK gene into an alpha or gamma 2 gene did not preclude the establishment of latent infections; (ii) there was no correlation between the levels of TK activity expressed in cell culture and the ability to establish latency; and (iii) rearrangement of the genome by insertions or deletions which interrupt gene domains did not automatically result in an inability to establish latent infections.</jats:p