Fatal Deterioration of a Respiratory Syncytial Virus Infection in an Infant with Abnormal Muscularization of Intra-Acinar Pulmonary Arteries: Autopsy and Histological Findings.

Respiratory syncytial virus (RSV) infection represents a global and noteworthy cause of hospitalization and death in infants of less than 1 year of age. The typical clinical manifestation is bronchiolitis, an inflammatory process of the small airways. The symptoms are usually a brief period of low-grade fever, cough, coryza, breathing difficulties, and reduced feeding. The progression of the disease is difficult to predict, even in previous healthy subjects. Symptoms may also be subtle and underestimated, thus leading to sudden unexpected infant death (SUID). In these cases, RSV infection is discovered at autopsy, either histologically or through real-time reverse transcription polymerase chain reaction (RT-PCR) performed on nasopharyngeal swabs. Herein, we describe a case of RSV infection in a 6-month-old infant with no risk factors, who rapidly deteriorated and unexpectedly died of respiratory insufficiency in a hospital setting. RT-PCR on nasopharyngeal swabs revealed RSV. The autopsy showed diffuse lymphogranulocytic bronchitis and bronchiolitis, and multiple foci of acute pneumonia. Abnormal muscularization of the intra-acinar pulmonary arteries was also observed, which likely contributed to worsening the lung impairment.

Neurally adjusted ventilatory assist in weaning of neonates affected by congenital diaphragmatic hernia.

OBJECTIVE: The aim of the study is to evaluate the application of neurally adjusted ventilatory assist (NAVA) in the respiratory weaning of patients affected by congenital diaphragmatic hernia (CDH). METHODS: We analyzed the NAVA weaning in 12 neonates affected by CDH, relating the effectiveness of the electrical activation of the diaphragm (EAdi) signal to the type of CDH repair (with or without patch), the size of the patch, the stomach and His angle position, and the trend evaluation of some cardiorespiratory parameters with NAVA compared to pressure-support-ventilation (PSV). RESULTS: 5 neonates submitted to primary repair showed a regular EAdi signal and were successfully weaned with NAVA. Of the seven patients submitted to patch repair, five operated with patch limited to the diaphragmatic postero-lateral area had an active EAdi signal that permitted weaning with NAVA. Only in two neonates with hemidiaphragm agenesis was NAVA not feasible due to the impossibility to capture the EAdi signal. Compared to PSV, NAVA allows a significant improvement of oxygenation-linked indexes and paCO2, while PIP is reduced. CONCLUSION: Neonatal CDH with a postero-lateral diaphragmatic defect allows the NAVA catheter to obtain a correct EAdi signal and develop a viable NAVA ventilation. The lower risk of lung injury in NAVA appears compatible with current ventilatory strategies considered useful in CDH.

Association of hepatitis C virus envelope proteins with exosomes.

As the human tetraspanin CD81 binds hepatitis C virus (HCV) envelope glycoprotein E2, we addressed the role CD81 may play in cellular trafficking of HCV envelope proteins. Studies on HCV life cycle are complicated by the lack of a robust cell culture system; we therefore transfected mammalian cells with HCV E1-E2 cDNA, with or without human CD81 (huCD81) cDNA. In the absence of huCD81, HCV envelope proteins are almost completely retained in the endoplasmic reticulum. Instead, when huCD81 is present, a fraction of HCV envelope proteins passes through the Golgi apparatus, matures acquiring complex sugars and is found extracellularly associated with exosomes. These are 60-100-nm membrane vesicles enriched in tetraspanins, released into the extracellular milieu by many cell types and having fusogenic activity. We also report that human plasma contains exosomes and that in HCV patients, viral RNA is associated with these circulating vesicles. We propose that the HCV-CD81 complex leaves cells in the form of exosomes, circulates in this form and exploits the fusogenic capabilities of these vesicles to infect cells even in the presence of neutralizing antibodies.

Expression of human CD81 in transgenic mice does not confer susceptibility to hepatitis C virus infection.

We previously demonstrated that hepatitis C virus (HCV) binds to human CD81 through the E2 glycoprotein. Therefore, expression of the human CD81 molecule in transgenic mice was expected to provide a new tool to study HCV infection in vivo, as the chimpanzee is the only species currently available as a laboratory animal model that can be infected with HCV. We produced transgenic mice expressing the human CD81 protein in a wide variety of tissues. We confirmed binding of recombinant E2 glycoprotein to the liver tissue as well as to thymocytes and splenic lymphocytes in the transgenic mice. We inoculated chimpanzee plasma infected with HCV into these animals. None of these transgenic animals showed evidence of viral replication. Furthermore, human CD81 transgenic mice that lack expression of endogenous mouse CD81 were also resistant to HCV infection. We conclude that expression of human CD81 alone is insufficient to confer susceptibility to HCV infection in the mouse. The presence of additional possible factors for HCV infection is discussed.