Interferon-Induced Transmembrane Protein 1 Regulates Endothelial Lumen Formation During Angiogenesis

OBJECTIVE: It is well established that angiogenesis is a complex and coordinated multi-step process. However, there remains a lack of information about the genes that regulate individual stages of vessel formation. Here, we aimed to define the role of human interferon-induced transmembrane protein 1 (IFITM1) during blood vessel formation. APPROACH AND RESULTS: We identified IFITM1 in a microarray screen for genes differentially regulated by endothelial cells (ECs) during an in vitro angiogenesis assay and found that IFITM1 expression was strongly induced as ECs sprouted and formed lumens. We showed by immunohistochemistry that human IFITM1 was expressed by stable blood vessels in multiple organs. siRNA-mediated knockdown of IFITM1 expression spared EC sprouting but completely disrupted lumen formation, both in vitro and in an in vivo xeno-transplant model. ECs lacking IFITM1 underwent early stages of lumenogenesis (i.e. intracellular vacuole formation) but failed to mature or expand lumens. Coimmunoprecipitation studies confirmed occludin as an IFITM1 binding partner in ECs and immunocytochemistry showed a lack of occludin at endothelial tight junctions in the absence of IFITM1. Finally, time-lapse video microscopy revealed that IFITM1 is required for the formation of stable cell-cell contacts during endothelial lumen formation. CONCLUSIONS: IFITM1 is essential for the formation of functional blood vessels and stabilizes EC-EC interactions during endothelial lumen formation by regulating tight junction assembly

They Might Be Giants: Does Syncytium Formation Sink or Spread HIV Infection?

International audienc

Neurological complications of human immunodeficiency virus infection.

The protean neurological manifestations of human immunodeficiency virus (HIV) infection are reviewed. Both the central nervous system and peripheral nervous system may be affected and many of the complications may occur in individuals with acquired immunodeficiency syndrome (AIDS)-related complex, or who are seropositive for HIV alone as well as those with the established AIDS syndrome. Specific therapy is available for certain of these neurological conditions, but the clinical course in others is untreatable and progressive. Although it seems likely that the pathogenesis of some of these syndromes such as the AIDS-dementia complex are due to the direct effect of HIV on the nervous system, in others the neurological injury probably occurs as a consequence of the immunosuppression which HIV induces, or immune-mediated mechanisms

Differences in the variability of cerebral proton magnetic resonance spectroscopy (1H-MRS) measurements within three HIV-infected cohorts.

INTRODUCTION Cerebral functional impairment remains prevalent in effectively treated HIV-infected subjects. As the results of formal cognitive testing are highly variable, surrogate markers to accurately measure cerebral function parameters are needed. Such markers include measurement of cerebral metabolite ratios (CMR) using proton magnetic resonance spectroscopy (1H-MRS). However, data on the inter-subject variability of CMR are sparse. Our aim was to assess inter-subject variability in CMRs within three different HIV-infected cohorts. METHODS Cerebral 1H-MRS was performed using a Phillips Achieva™ 1.5 Tesla magnetic resonance scanner in HIV-infected subjects as follows: 12 subjects before (group 1) and after intensification of antiretroviral therapy with maraviroc (group 2) and 13 subjects with acute viral hepatitis C (HCV) co-infection (group 3). The coefficients of variation (CV) for CMRs in each group were determined and compared using non-parametric tests to determine whether the inter-subject variability differed significantly. All baseline characteristics between the groups were similar. RESULTS Overall CVs for all CMRs in groups 1, 2 and 3 were 32.3%, 33.2% and 23.4%, respectively (group 1 vs. 2, p=0.863; group 1 vs. 3, p=0.076). On testing for differences in variability between individual CMRs, two metabolites in the right basal ganglia (RBG) had statistically significantly different CVs when comparing group 1 with group 3: N-acetyl aspartate/creatine (NAA/Cr), p=0.029 and myo-Inositol/creatine (mI/Cr), p=0.016. CONCLUSION The variability of 1H MRS-measurable CMRs in HIV-infected individuals was lower in those with acute HCV co-infection (group 3).We can conclude that the use of these CMRs in 1H MRS imaging in patients with HIV/acute HCV co-infection is more reliable to assess cerebral function than in patients with HIV infection alone. This has implications for future sample size estimations