Single-Cell Analysis Uncovers a Vast Diversity in Intracellular Viral Defective Interfering RNA Content Affecting the Large Cell-to-Cell Heterogeneity in Influenza A Virus Replication.

Virus replication displays a large cell-to-cell heterogeneity; yet, not all sources of this variability are known. Here, we study the effect of defective interfering (DI) particle (DIP) co-infection on cell-to-cell variability in influenza A virus (IAV) replication. DIPs contain a large internal deletion in one of their eight viral RNAs (vRNA) and are, thus, defective in virus replication. Moreover, they interfere with virus replication. Using single-cell isolation and reverse transcription polymerase chain reaction, we uncovered a large between-cell heterogeneity in the DI vRNA content of infected cells, which was confirmed for DI mRNAs by single-cell RNA sequencing. A high load of intracellular DI vRNAs and DI mRNAs was found in low-productive cells, indicating their contribution to the large cell-to-cell variability in virus release. Furthermore, we show that the magnitude of host cell mRNA expression (some factors may inhibit virus replication), but not the ribosome content, may further affect the strength of single-cell virus replication. Finally, we show that the load of viral mRNAs (facilitating viral protein production) and the DI mRNA content are, independently from one another, connected with single-cell virus production. Together, these insights advance single-cell virology research toward the elucidation of the complex multi-parametric origin of the large cell-to-cell heterogeneity in virus infections.

Multiferroic Hysteresis Loop.

Multiferroics, showing both ferroelectric and magnetic order, are promising candidates for future electronic devices. Especially, the fundamental understanding of ferroelectric switching is of key relevance for further improvements, which however is rarely reported in literature. On a prime example for a spin-driven multiferroic, LiCuVO4, we present an extensive study of the ferroelectric order and the switching behavior as functions of external electric and magnetic fields. From frequency-dependent polarization switching and using the Ishibashi-Orihara theory, we deduce the existence of ferroelectric domains and domain-walls. These have to be related to counterclockwise and clockwise spin-spirals leading to the formation of multiferroic domains. A novel measurement-multiferroic hysteresis loop-is established to analyze the electrical polarization simultaneously as a function of electrical and magnetic fields. This technique allows characterizing the complex coupling between ferroelectric and magnetic order in multiferroic LiCuVO4.

Dielectric properties and electrical switching behaviour of the spin-driven multiferroic LiCuVO4.

The simultaneous existence and coupling of ferroelectric and magnetic ordering in a material, so-called multiferroicity, is of great scientific interest due to the underlying complex physical mechanisms and its possible applications. Here we present the multiferroic properties of a prototypical spin-driven ferroelectric material, the spin-1/2 chain cuprate LiCuVO4. In this system, spiral spin order, with propagation in the b direction and a spin helix in the ab plane, induces ferroelectric polarization in the a direction when no magnetic field is applied. In an external magnetic field, the direction of the spin spiral and thus the direction of the electrical polarization can be switched. Broadband dielectric spectroscopy on a single crystalline sample oriented in two different directions was performed in applied external magnetic fields up to 9 T, demonstrating this switching behaviour of the ferroelectric polarization. Furthermore, detailed magnetic-field and temperature-dependent ferroelectric hysteresis-loop measurements reveal the switching of polarization by an electrical field, which implies the electric control of the spin helicity of LiCuVO4.