Helminth extracellular vesicles co-opt host monocytes to drive T cell anergy.

Parasitic helminths secrete extracellular vesicles (EVs) into their host tissues to modulate immune responses, but the underlying mechanisms are poorly understood. We demonstrate that Ascaris EVs are efficiently internalised by monocytes in human peripheral blood mononuclear cells and increase the percentage of classical monocytes. Furthermore, EV treatment of monocytes induced a novel anti-inflammatory phenotype characterised by CD14, CD16, CC chemokine receptor 2 (CCR2) and programmed death-ligand 1 (PD-L1) cells.

CD46 Isoforms Influence the Mode of Entry by Human Herpesvirus 6A/B in T Cells.

CD46 is a receptor for human herpesvirus 6A (HHV-6A) and is in some cells also important for infection with HHV-6B. CD46 has several isoforms of which the most commonly expressed can be distinguished by expression of a BC domain or a C domain in a serine-threonine-proline-rich (STP) extracellular region. Using a SupT1 CD46 CRISPR-Cas9 knockout model system reconstituted with specific CD46 isoforms, we demonstrated that HHV-6A infection was more efficient when BC isoforms were expressed as opposed to C isoforms, measured by higher levels of intracellular viral transcripts and recovery of more progeny virus.

The tetraspanin protein CD9 modulates infection with human herpesvirus 6A and 6B in a CD46-dependent manner.

Tetraspanins are four-span transmembrane proteins that organize the membrane by forming tetraspanin-enriched microdomains. These have been shown to be important for virus entry. The human herpesvirus (HHV)-6A receptor CD46 is known to form complexes with the tetraspanin CD9 and β1-integrins, however the significance of this for HHV-6A infection remains unexplored.

Divergent tropism of HHV-6A and HHV-6B in T cells expressing different CD46 isoform patterns.

CD46 is a receptor for HHV-6A, but its role as a receptor for HHV-6B is controversial. The significance of CD46 isoforms for HHV-6A and HHV-6B tropism is unknown. HHV-6A was able to initiate transcription of the viral genes U7 and U23 in the CD46CD134 T-cell lines Peer, Jurkat, Molt3, and SupT1, whereas HHV-6B was only able to do so in Molt3 and SupT1, which expressed a CD46 isoform pattern different from Peer and Jurkat.