The Hsf1-sHsp cascade has pan-antiviral activity in mosquito cells.

Aedes mosquitoes transmit pathogenic arthropod-borne (arbo) viruses, putting nearly half the world's population at risk. Blocking virus replication in mosquitoes is a promising approach to prevent arbovirus transmission, the development of which requires in-depth knowledge of virus-host interactions and mosquito immunity. By integrating multi-omics data, we find that heat shock factor 1 (Hsf1) regulates eight small heat shock protein (sHsp) genes within one topologically associated domain in the genome of the Aedes aegypti mosquito.

The DEAD-box RNA helicase Dhx15 controls glycolysis and arbovirus replication in Aedes aegypti mosquito cells.

Aedes aegypti mosquitoes are responsible for the transmission of arthropod-borne (arbo)viruses including dengue and chikungunya virus (CHIKV) but in contrast to human hosts, arbovirus-infected mosquitoes are able to efficiently control virus replication to sub-pathological levels. Yet, our knowledge of the molecular interactions of arboviruses with their mosquito hosts is incomplete. Here, we aimed to identify and characterize novel host genes that control arbovirus replication in Aedes mosquitoes.

Genetic determinants of antiviral immunity in dipteran insects - Compiling the experimental evidence.

The genetic basis of antiviral immunity in dipteran insects is extensively studied in Drosophila melanogaster and advanced technologies for genetic manipulation allow a better characterization of immune responses also in non-model insect species. Especially, immunity in vector mosquitoes is recently in the spotlight, due to the medical impact that these insects have by transmitting viruses and other pathogens. Here, we review the current state of experimental evidence that supports antiviral functions for immune genes acting in different cellular pathways.

Defective Interferon Gamma Production by Tumor-Specific CD8 T Cells Is Associated With 5'Methylcytosine-Guanine Hypermethylation of Interferon Gamma Promoter.

Interferon gamma (IFNγ) supports effector responses of CD8 cytotoxic T lymphocytes (CTLs) and is a surrogate marker for detection of antigen-specific T cells. Here, we show that tumor-specific CTL clones have impaired IFNγ expression and production upon activation. Assessment of the relationship between IFNγ production and the 5'methylcytosine-guanine (CpG) dinucleotide methylation of the IFNγ promoter using bisulfite treatment has shown that IFNγ CTL clones accumulates CpG hypermethylation within the promoter at key transcription factor binding sites (-186 and -54), known to be vital for transcription.

Self-Maintaining CD103 Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses.

Enrichment of CD103 tumor-infiltrating T lymphocytes (TIL) is associated with improved outcomes in patients. However, the characteristics of human CD103 cytotoxic CD8 T cells (CTL) and their role in tumor control remain unclear. We investigated the features and antitumor mechanisms of CD103 CTLs by assessing T-cell receptor (TCR)-matched CD103 and CD103 cancer-specific CTL immunity and its immunophenotype Interestingly, we found that differentiated CD103 cancer-specific CTLs expressed the active form of TGFβ1 to continually self-regulate CD103 expression, without relying on external TGFβ1-producing cells.

Therapeutic Monoclonal Antibodies for Ebola Virus Infection Derived from Vaccinated Humans.

We describe therapeutic monoclonal antibodies isolated from human volunteers vaccinated with recombinant adenovirus expressing Ebola virus glycoprotein (EBOV GP) and boosted with modified vaccinia virus Ankara. Among 82 antibodies isolated from peripheral blood B cells, almost half neutralized GP pseudotyped influenza virus. The antibody response was diverse in gene usage and epitope recognition.