Nipah virus (NiV) is a zoonotic biosafety level 4 paramyxovirus that emerged recently in Asia with high mortality in man. NiV is a member, with Hendra virus (HeV), of the Henipavirus genus in the Paramyxoviridae family. Although NiV entry, like that of other paramyxoviruses, is believed to occur via pH-independent fusion with the host cell's plasma membrane we present evidence that entry can occur by an endocytic pathway. The NiV receptor ephrinB2 has receptor kinase activity and we find that ephrinB2's cytoplasmic domain is required for entry but is dispensable for post-entry viral spread. The mutation of a single tyrosine residue (Y304F) in ephrinB2's cytoplasmic tail abrogates NiV entry. Moreover, our results show that NiV entry is inhibited by constructions and drugs specific for the endocytic pathway of macropinocytosis. Our findings could potentially permit the rapid development of novel low-cost antiviral treatments not only for NiV but also HeV.
Introduction:Vitamin D (VD) deficiency is a major public health problem worldwide. In spite of its high prevalence, particularly among elderly people, VD deficiency is still underestimated by many physicians. Increasingly, VD deficiency is associated with several known geriatric syndromes.Methods:The study sample consisted of 125 patients, aged 75 years and older, admitted to the acute geriatric unit. The plausible association between the serum 25-hydroxyvitamin D [25(OH)D] level and patient age, sex, body mass index, renal function, cholecystectomy history, and the prescribed drugs had been investigated. The Fisher's exact test was used to conduct the statistical analysis of data.Results:Surprisingly, furosemide treatment was correlated with normal 25(OH)D levels and an increased incidence of secondary hyperparathyroidism. Unlike the other four parameters mentioned above, our data showed that only the patient sex exhibited a significant association with 25(OH)D level as elderly males suffered from a serious VD deficiency as compared to elderly females.Conclusion:Old age is an independent risk factor for VD deficiency. The supplementary dose of VD should be precisely defined to achieve the optimal serum 25(OH)D level in elderly people. The definition of the normal serum 25(OH)D threshold in elderly furosemide-treated patients is worth of further studies.
Gene transfer into quiescent T and B cells is important for gene therapy and immunotherapy approaches. Previously, we generated lentiviral vectors (LVs) pseudotyped with Edmonston (Ed) measles virus (MV) hemagglutinin (H) and fusion (F) glycoproteins (H/F-LVs), which allowed efficient transduction of quiescent human T and B cells. However, a major obstacle in the use of H/F-LVs in vivo is that most of the human population is vaccinated against measles. As the MV humoral immune response is exclusively directed against the H protein of MV, we mutated the two dominant epitopes in H, Noose, and NE. LVs pseudotyped with these mutant H-glycoproteins escaped inactivation by monoclonal antibodies (mAbs) but were still neutralized by human serum. Consequently, we took advantage of newly emerged MV-D genotypes that were less sensitive to MV vaccination due to a different glycosylation pattern. The mutation responsible was introduced into the H/F-LVs, already mutated for Noose and NE epitopes. We found that these mutant H/F-LVs could efficiently transduce quiescent lymphocytes in the presence of high concentrations of MV antibody-positive human serum. Finally, upon incubation with total blood, mimicking the in vivo situation, the mutant H/F-LVs escaped MV antibody neutralization, where the original H/F-LVs failed. Thus, these novel H/F-LVs offer perspectives for in vivo lymphocyte-based gene therapy and immunotherapy.
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