Wenk MR

A T164S mutation in the dengue virus NS1 protein is associated with greater disease severity in mice

Published date : 26 Jun 2019

Dengue viruses cause severe and sudden human epidemics worldwide. The secreted form of the nonstructural protein 1 (sNS1) of dengue virus causes vascular leakage, a hallmark of severe dengue disease. Here, we reverse engineered the T164S mutation of NS1, associated with the severity of dengue epidemics in the Americas, into a dengue virus serotype 2 mildly infectious strain. The T164S mutant virus decreased infectious virus production and increased sNS1 production in mammalian cell lines and human peripheral blood mononuclear cells (PBMCs) without affecting viral RNA replication.

type
Journal Paper
journal
Science Translational Medicine, 26 Jun 2019, Vol. 11, Issue 498, doi: 10.1126/scitranslmed.aat772
Impact Factor
16.796

Homozygous mutation in MFSD2A, encoding a lysolipid transporter for docosahexanoic acid, is associated with microcephaly and hypomyelination

Published date : 24 Jul 2018

The major facilitator superfamily domain-containing protein 2A (MFSD2A) is a constituent of the blood-brain barrier and functions to transport lysophosphatidylcholines (LPCs) into the central nervous system. LPCs such as that derived from docosahexanoic acid (DHA) are indispensable to neurogenesis and maintenance of neurons, yet cannot be synthesized within the brain and are dependent on MFSD2A for brain uptake. Recent studies have implicated MFSD2A mutations in lethal and non-lethal microcephaly syndromes, with the severity correlating to the residual activity of the transporter.

type
Journal Paper
journal
Neurogenetics 2018 Jul 24. doi: 10.1007/s10048-018-0556-6
Impact Factor
3.09