ORF50, an immediate-early gene of human herpesvirus-8 (HHV-8), encodes a transactivating protein necessary for virus reactivation and lytic replication. ORF50 was reported recently to synergize with human immunodeficiency virus type 1 (HIV-1) tat at a post-transcriptional level. To study the effects of these molecular interactions on HIV replication and biology, cellular clones stably transformed with ORF50 were obtained by transfection of cell lines of different origin. These clones were infected subsequently with HIV. Experiments showed that ORF50 enhances HIV replication in T and B cells (Jurkat and BC-3 cells) and induces susceptibility and transient permissiveness in non-susceptible glial (A172) cells. Upregulation of viral receptors and co-receptors did not account for increased sensitivity to HIV infection and therefore the action of ORF50 might be modulated by the intracellular environment. Interestingly, non-susceptible cells transformed with ORF50 showed transient production of HIV particles that could spread to adjacent cells by direct contact. These findings show that HHV-8 ORF50 has an enhancing effect on HIV replication in vitro and suggest that the two viruses might interact in co-infected patients.

The results suggest that reciprocal molecular interactions between human and porcine herpesviruses might occur in vivo, and support the hypothesis that PLHV-1 might have pathogenic relevance in the course of xenotransplantation.

Background Retinoids have a pronounced antiviral effect against several viruses. In this study we aimed to investigate the effect of retinoids on human herpesvirus 8 (HHV-8). Methods A panel of retinoic acid compounds were tested for their antiviral activity against HHV-8 in human umbilical vascular endothelial cells (HUVECs) and in a human epithelial cell line. The presence, transcription and antigen expression of HHV-8 in infected cells – in the presence or absence of retinoic acid compounds – were evaluated by PCR, reverse transcriptase PCR and immunofluorescence assays; HHV-8 viral load was determined by real-time quantitative PCR. Angiogenesis induced by HHV-8 was also assessed using Cultrex® basement membrane extract. Results The compounds tested specifically inhibited viral promoters, during the early and late phases of infection in both cell systems tested, and resulted in up to 100fold reduction of viral titre and release of progeny virus. The inhibition of viral replication induced by retinoids in endothelial cells, the primary target of HHV-8-driven transformation in Kaposi's Sarcoma, prevented endothelial cells from developing spindle morphology and in vitro tube formation, characteristic changes associated with HHV-8 infection and transformation. Conclusions We show that retinoids inhibit HHV-8 replication and identify new retinoid compounds with a strong antiviral effect. Selective retinoids, particularly those with retinoic acid receptor agonist activity, may be good candidates for the development of antiviral drugs.

ObjectivesFrom the first description by Leo Kanner [1], autism has been an enigmatic neurobehavioral phenomenon. The new genetic/genomic technologies of the past decade have not been as productive as originally anticipated in unveiling the mysteries of autism. The specific etiology of the majority of cases of autism spectrum disorder (ASD) is unknown, although numerous genetic/genomic variants and alterations of diverse cellular functions have been reported. Prompted by this failure, we have investigated whether the metabolomics approach might yield results which could simultaneously lead to a blood-based screening/diagnostic test and to treatment options. Methods Plasma samples from a clinically well-defined cohort of 100 male individuals, ages 2-16+ years, with ASD and 32 age-matched typically developing (TD) controls were subjected to global metabolomic analysis. ResultsWe have identified more than 25 plasma metabolites among the approximately 650 metabolites analyzed, representing over 70 biochemical pathways, that can discriminate children with ASD as young as 2 years from children that are developing typically. The discriminating power was greatest in the 2-10 year age group and weaker in older age groups. The initial findings were validated in a second cohort of 83 children, males and females, ages 2-10 years, with ASD and 76 age and gender-matched TD children. The discriminant metabolites were associated with several key biochemical pathways suggestive of potential contributions of increased oxidative stress, mitochondrial dysfunction, inflammation and immune dysregulation in ASD. Further, targeted quantitative analysis of a subset of discriminating metabolites using tandem mass spectrometry provided a reliable laboratory method to detect children with ASD. Conclusion Metabolic profiling appears to be a robust technique to identify children with ASD ages 2-10 years and provides insights into the altered metabolic pathways in ASD, which could lead to treatment strategies. ObjectivesTo uncover novel traits associated with nicotine and alcohol use genetics, we performed a phenome-wide association study in a large multi-ethnic cohort. Methods We investigated 7,688 African-Americans (AFR), 1,133 Asian-Americans (ASN), 14,081 European-Americans (EUR), and 3,492 Hispanic-Americans (HISP) from the Women's Health Initiative, analyzing risk alleles located in the CHRNA5-CHRNA3 locus (rs8034191, rs1051730, rs12914385, rs2036527, and rs16969968) for nicotine-related traits and ADH1B (rs1229984 and rs2066702) and ALDH2 (rs671) for alcohol-related traits with respect to anthropometric characteristics, dietary habits, social status, psychological circumstances, reproductive history, health conditions, and nicotine-and alcohol-related traits. ResultsThe investigated loci resulted associated with novel traits: rs1229984 were associated with family income (p=4.1*10 −12 ), having a pet (p=6.5*10 −11 ), partner education (p=1.8*10 −10 ), "usually expect the best" (p=2.4*10 −7), "felt calm and peaceful" (p=2.6*10 ), and num...

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