Mutation of UL24 impedes the dissemination of acute herpes simplex virus 1 infection from the cornea to neurons of trigeminal ganglia.

Herpes simplex virus 1 (human herpesvirus 1) initially infects epithelial cells of the mucosa and then goes on to infect sensory neurons leading ultimately to a latent infection in trigeminal ganglia (TG). UL24 is a core herpesvirus gene that has been identified as a determinant of pathogenesis in several Alphaherpesvirinae, although the underlying mechanisms are unknown. In a mouse model of ocular infection, a UL24-deficient virus exhibited a reduction in viral titres in tear films of 1 log10, whilst titres in TG are often below the level of detection. Moreover, the efficiency of reactivation from latency was also severely reduced. Herein, we investigated how UL24 contributed to acute infection of TG. Our results comparing the impact of UL24 on viral titres in eye tissue versus in tear films did not reveal a general defect in virus release from the cornea. We also found that the impairment of replication seen in mouse primary embryonic neurons with a UL24-deficient virus was not more severe than that observed in an epithelial cell line. Rather, in situ histological analyses revealed that infection with a UL24-deficient virus led to a significant reduction in the number of acutely infected neurons at 3 days post-infection (p.i.). Moreover, there was a significant reduction in the number of neurons positive for viral DNA at 2 days p.i. for the UL24-deficient virus as compared with that observed for WT or a rescue virus. Our results supported a model whereby UL24 functions in the dissemination of acute infection from the cornea to neurons in TG.

Involvement of the UL24 protein in herpes simplex virus 1-induced dispersal of B23 and in nuclear egress.

UL24 of herpes simplex virus 1 (HSV-1) is widely conserved within the Herpesviridae family. Herein, we tested the hypothesis that UL24, which we have previously shown to induce the redistribution of nucleolin, also affects the localization of the nucleolar protein B23. We found that HSV-1-induced dispersal of B23 was dependent on UL24. The conserved N-terminal portion of UL24 was sufficient to induce the redistribution of B23 in transient transfection assays. Mutational analysis revealed that the endonuclease motif of UL24 was important for B23 dispersal in both transfected and infected cells. Nucleolar protein relocalization during HSV-1 infection was also observed in non-immortalized cells. Analysis of infected cells by electron microscopy revealed a decrease in the ratio of cytoplasmic versus nuclear viral particles in cells infected with a UL24-deficient strain compared to KOS-infected cells. Our results suggest that UL24 promotes nuclear egress of nucleocapsids during HSV-1 infection, possibly though effects on nucleoli.

Free flap reconstruction in the head and neck region following radiotherapy: a cohort study identifying negative outcome predictors.

BACKGROUND: With the increased use of radiotherapy in the treatment of head and neck cancers, free tissue transfer in an irradiated field is now common. Reported outcomes with free tissue transfer reconstructions in irradiated areas are often unclear and contradictory. This is attributable in part to small sample size and heterogeneity in patients and procedures. The goals of this study were, first, to determine the outcome of head and neck reconstructions in an irradiated field using a large retrospective cohort and, second, to identify negative outcome predictors that could potentially be modified to reduce the morbidity in these procedures. METHODS: Patients undergoing free flap reconstruction in irradiated head and neck regions between July of 2005 and July of 2007 were identified. Charts, including operative and radiotherapy records, were reviewed. Multiple logistic regressions were performed to identify negative outcome predictors. RESULTS: During the study period at the authors' institution, 984 patients underwent head and neck free flap reconstruction. Of these, 137 had free tissue transferred to irradiated fields. Patients received an average radiotherapy dose of 64.5 Gy. The overall flap success rate was 96.4 percent. The postoperative complication rate was 47 percent. There was an overall 22 percent reoperation rate and a 28 percent infection rate. Segmental mandibulectomy, larger flap size, and infection were found to be significant negative outcome predictors. CONCLUSIONS: This study confirms that free flap transfer to previously irradiated head and neck areas has a success rate comparable to that of transfer to nonirradiated zones. However, previously irradiated patients have a high risk of complications. Infection, as a modifiable risk factor, should be treated aggressively.

Effects of compressive vests on pulmonary function of infants with thoracic burn scars.

OBJECTIVE: To prospectively evaluate the effects of compressive vests on the pulmonary function of infants with thoracic burn scars. METHODS: Between April 2000 and October 2005, all infants aged 2 years or less and all those aged between 2 and 3 years if they had concomitant pulmonary pathology, who were in need of a compressive vest for the treatment of burn scars to the thorax, underwent comparative pulmonary function testing under sedation with the vest closed and then opened. RESULTS: Of the 23 infants who met the inclusion criteria, 19 had complete data. There were significant differences in oxygen saturation, respiratory rate, tidal volume/kg body weight, respiratory compliance and peak tidal expiratory flow /tidal volume, with or without vest compression. CONCLUSIONS: Compressive vests used at our centre to treat thoracic burn scars of infants aged 2 years or less, and those aged between 2 and 3 years with concomitant pulmonary pathology, did have a statistically significant effect on their pulmonary function, but this did not translate into clinically significant differences. However, the differences observed might become clinically significant in the presence of pulmonary comorbidity or severe burns. Routine pulmonary function testing before the use of vest compression might thus benefit these infants.