Prevention of measles virus infection by intranasal delivery of fusion inhibitor peptides.

UNLABELLED: Measles virus (MV) infection is undergoing resurgence and remains one of the leading causes of death among young children worldwide despite the availability of an effective measles vaccine. MV infects its target cells by coordinated action of the MV H and the fusion (F) envelope glycoprotein; upon receptor engagement by H, the prefusion F undergoes a structural transition, extending and inserting into the target cell membrane and then refolding into a postfusion structure that fuses the viral and cell membranes. By interfering with this structural transition of F, peptides derived from the heptad-repeat (HR) regions of F can potently inhibit MV infection at the entry stage. We show here that specific features of H's interaction with its receptors modulate the susceptibility of MV F to peptide fusion inhibitors. A higher concentration of inhibitory peptides is required to inhibit F-mediated fusion when H is engaged to its nectin-4 receptor than when H is engaged to its CD150 receptor. Peptide inhibition of F may be subverted by continued engagement of receptor by H, a finding that highlights the ongoing role of H-receptor interaction after F has been activated and that helps guide the design of more potent inhibitory peptides. Intranasal administration of these peptides results in peptide accumulation in the airway epithelium with minimal systemic levels of peptide and efficiently prevents MV infection in vivo in animal models. The results suggest an antiviral strategy for prophylaxis in vulnerable and/or immunocompromised hosts. IMPORTANCE: Measles virus (MV) infection causes an acute illness that may be associated with infection of the central nervous system (CNS) and severe neurological disease. No specific treatment is available. We have shown that parenterally delivered fusion-inhibitory peptides protect mice from lethal CNS MV disease. Here we show, using established small-animal models of MV infection, that fusion-inhibitory peptides delivered intranasally provide effective prophylaxis against MV infection. Since the fusion inhibitors are stable at room temperature, this intranasal strategy is feasible even outside health care settings, could be used to protect individuals and communities in case of MV outbreaks, and could complement global efforts to control measles.

Clinical significance of intracranial developmental venous anomalies.

OBJECTIVES: Venous angiomas, or developmental venous anomalies (DVAs), represent the most often occurring cerebral vascular malformation. The clinical significance of a DVA is, however, at present unclear. METHODS: A retrospective analysis was carried out on two series of consecutive cranial MRIs performed between January 1990 and August 1996 in a university department of neuroradiology and in a large radiological private practice. The medical records of all patients in whom a DVA was diagnosed were screened to identify the specific complaint which necessitated the imaging procedure. RESULTS: A total of 67 patients with DVA could be identified. In 12 patients an associated cavernoma was found. The main reason for performing the MRI was the evaluation of seizures or of headaches. In all patients with DVA in whom an intracerebral haemorrhage was diagnosed an associated cavernoma was present at the site of the haemorrhage. None of the 67 patients showed an association between the complaints that led to the MRI and the location of the DVA. CONCLUSIONS: DVAs do not seem to be associated with a specific clinical presentation. In a significant percentage of cases, however, coexisting cavernomas are found which have a defined bleeding potential and should be treated independently of the DVA. This study supports the hypothesis that DVAs are a congenital abnormality of venous drainage without clinical significance.

Case 11, Part 2. Angiokeratoma corporis diffusum (Fabry's disease).

A case of Fabry's disease is reported. The patient had multiple supernumerary, impacted, and unerupted teeth and other developmental abnormalities of the facial skeleton. The patient tolerated surgical removal of impacted and unerupted teeth without complications. However, this did not relieve the facial pain. The expected prognosis of this patient will be a continued vascular and renal degeneration with death probable before the age of 50 years if the disease is untreated. Currently, the patient is being considered as a possible candidate for renal transplantation.