| 1. |
- Hait, A. S., et al.
(författare)
-
Defects in LC3B2 and ATG4A underlie HSV2 meningitis and reveal a critical role for autophagy in antiviral defense in humans
- 2020
-
Ingår i: Science Immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 5:54
-
Tidskriftsartikel (refereegranskat)abstract
- Recurrent herpesvirus infections can manifest in different forms of disease, including cold sores, genital herpes, and encephalitis. There is an incomplete understanding of the genetic and immunological factors conferring susceptibility to recurrent herpes simplex virus 2 (HSV2) infection in the central nervous system (CNS). Here, we describe two adult patients with recurrent HSV2 lymphocytic Mollaret's meningitis that each carry a rare monoallelic variant in the autophagy proteins ATG4A or LC3B2. HSV2-activated autophagy was abrogated in patient primary fibroblasts, which also exhibited significantly increased viral replication and enhanced cell death. HSV2 antigen was captured in autophagosomes of infected cells, and genetic inhibition of autophagy by disruption of autophagy genes, including ATG4A and LC3B2, led to enhanced viral replication and cell death in primary fibroblasts and a neuroblastoma cell line. Activation of autophagy by HSV2 was sensitive to ultraviolet (UV) irradiation of the virus and inhibited in the presence of acyclovir, but HSV2-induced autophagy was independent of the DNA-activated STING pathway. Reconstitution of wild-type ATG4A and LC3B2 expression using lentiviral gene delivery or electroporation of in vitro transcribed mRNA into patient cells restored virus-induced autophagy and the ability to control HSV2 replication. This study describes a previously unknown link between defective autophagy and an inborn error of immunity that can lead to increased susceptibility to HSV2 infection, suggesting an important role for autophagy in antiviral immunity in the CNS.
|
|
| 2. |
- Husain, S., et al.
(författare)
-
Large Dzyaloshinskii-Moriya interaction and atomic layer thickness dependence in a ferromagnet- WS2 heterostructure
- 2022
-
Ingår i: Physical Review B. - : American Physical Society. - 2469-9950 .- 2469-9969. ; 105:6
-
Tidskriftsartikel (refereegranskat)abstract
- Two-dimensional transition metal dichalcogenides (TMDs) have immense potential for spintronics applications. Here, we report atomic layer thickness dependence in WS2/Co3FeB heterostructures. The layer dependence is predicted by density functional theory and demonstrated experimentally by the layer dependence of the Dzyaloshinskii-Moriya interaction (DMI). Notably, we have observed the DMI in WS2 to be larger than that for heavy metals such as W and Ta, which is important to stabilize chiral structures. Inversion symmetry is not preserved with an odd number of layers, while it exists with an even number of layers. This symmetry rule is reflected in the temperature dependence of the effective damping parameter of the heterostructure. That the damping parameter decreases (increases) in odd (even) layers can be resolved at low temperature. This suggests that the layer dependence has its origin at the WS2 interface, where the spin-valley coupling and spin-orbit coupling activate these features. Large DMI, pure spin current, and unique layer dependence in TMDs provide valuable information and fundamental understanding for designing TMD-based quantum information storage devices. © 2022 American Physical Society.
|
|
