Impact of Thymectomy on the Peripheral T Cell Pool in the Context of SIV Infection

The thymus is the primary lymphoid organ responsible for T cell production. It is of particular interest in the context of human immunodeficiency virus (HIV)-l infection, in which the progressive loss of CD4+ T cells leads to immunodeficiency and opportunistic infection. CD4+ T cell loss is thought to result from direct and indirect killing of C D 4 cells in the periphery as well as from pathogenic effects of the virus on the thymus. However, it is not fully understood which is the greater factor in viral-induced CD4+ T cell decay. The development of an assay to detect T cell receptor excisional circles (TREC) as a marker for recent T cell receptor (TCR) recombination in the thymus has proved to be an invaluable tool for the study of recent thymic emigrants. Here we describe the development of this technique in the rhesus macaque model and use this method in combination with other techniques to study the role of the thymus in maintenance of the peripheral T cell pool. This study has two major goals: to define the role of the thymus in peripheral T cell homeostasis in the juvenile rhesus macaque (Macaca mulatto) and to assess the significance of thymic output in the context of simian immunodeficiency virus (SIV) infection. To this end, we have studied the impact of surgical thymectomy on the peripheral T cell pool in a cohort of macaques. W e present evidence that thymic output in the juvenile macaque is measurable but quantitatively insignificant in the context of the total T cell pool. While SIV infection does have pathogenic effects on the thymus, these effects play a minimal role in the overall destruction of the peripheral T cell pool

Voriconazole-associated cutaneous malignancy: a literature review on photocarcinogenesis in organ transplant recipients.

This article synthesizes the current data regarding the implication of voriconazole in the development of skin cancer in organ transplant recipients (OTRs) and offers suggestions for additional research. According to Organ Procurement and Transplantation Network data, 28 051 solid organ transplants were performed in 2012. Due to advancements in immunosuppression and management of infectious diseases, survival of OTRs has substantially increased. Voriconazole is a widely prescribed antifungal medication used for prophylaxis and for treatment of invasive fungal infections in OTRs. Case reports describing skin cancer associated with voriconazole exposure emerged shortly after US Food and Drug Administration approval of the drug, and it is now established that voriconazole is an independent risk factor for the development of cutaneous malignancy in lung transplant recipients. The mechanism of voriconazole-induced skin cancer is still unknown and may involve its primary metabolite, voriconazole N-oxide. Here we discuss the current data and potential mechanisms of voriconazole-associated photosensitivity and carcinogenesis and identify areas that require further research

Validation of a Diagnostic Microarray for Human Papillomavirus: Coverage of 102 Genotypes

Papillomaviruses have been implicated in a variety of human diseases ranging from common warts to invasive carcinoma of the anogenital mucosa. Existing assays for genotyping human papillomavirus are restricted to a small number of types. Here, we present a comprehensive, accurate microarray strategy for detection and genotyping of 102 human papillomavirus types and validate its use in a panel of 91 anal swabs. This array has equal performance to traditional dot blot analysis with the benefits of added genotype coverage and the ability to calibrate readout over a range of sensitivity or specificity values

Human Skin Microbiota: High Diversity of DNA Viruses Identified on the Human Skin by High Throughput Sequencing

The human skin is a complex ecosystem that hosts a heterogeneous flora. Until recently, the diversity of the cutaneous microbiota was mainly investigated for bacteria through culture based assays subsequently confirmed by molecular techniques. There are now many evidences that viruses represent a significant part of the cutaneous flora as demonstrated by the asymptomatic carriage of beta and gamma-human papillomaviruses on the healthy skin. Furthermore, it has been recently suggested that some representatives of the Polyomavirus genus might share a similar feature. In the present study, the cutaneous virome of the surface of the normal-appearing skin from five healthy individuals and one patient with Merkel cell carcinoma was investigated through a high throughput metagenomic sequencing approach in an attempt to provide a thorough description of the cutaneous flora, with a particular focus on its viral component. The results emphasize the high diversity of the viral cutaneous flora with multiple polyomaviruses, papillomaviruses and circoviruses being detected on normal-appearing skin. Moreover, this approach resulted in the identification of new Papillomavirus and Circovirus genomes and confirmed a very low level of genetic diversity within human polyomavirus species. Although viruses are generally considered as pathogen agents, our findings support the existence of a complex viral flora present at the surface of healthy-appearing human skin in various individuals. The dynamics and anatomical variations of this skin virome and its variations according to pathological conditions remain to be further studied. The potential involvement of these viruses, alone or in combination, in skin proliferative disorders and oncogenesis is another crucial issue to be elucidated