10 Questions and 4 experts on Corona: Answers by Akiko Iwasaki, Gérard Krause, Samuel Alizon, and Rino Rappuoli.

A multi-person interview on the unrolling corona pandemic with Samuel Alizon, Akiko Iwasaki, Gerard Krause and Rino Rappuoli.

Dietary alterations modulate susceptibility to Plasmodium infection.

The relevance of genetic factors in conferring protection to severe malaria has been demonstrated, as in the case of sickle cell trait and G6PD deficiency . However, it remains unknown whether environmental components, such as dietary or metabolic variations, can contribute to the outcome of infection . Here, we show that administration of a high-fat diet to mice for a period as short as 4 days impairs Plasmodium liver infection by over 90%.

Genomic variation in two gametocyte non-producing Plasmodium falciparum clonal lines.

Background: Transmission of the malaria parasite Plasmodium falciparum from humans to the mosquito vector requires differentiation of a sub-population of asexual forms replicating within red blood cells into non-dividing male and female gametocytes. The nature of the molecular mechanism underlying this key differentiation event required for malaria transmission is not fully understood.

Methods: Whole genome sequencing was used to examine the genomic diversity of the gametocyte non-producing 3D7-derived lines F12 and A4.

Genome-wide RIP-Chip analysis of translational repressor-bound mRNAs in the Plasmodium gametocyte.

Background: Following fertilization, the early proteomes of metazoans are defined by the translation of stored but repressed transcripts; further embryonic development relies on de novo transcription of the zygotic genome. During sexual development of Plasmodium berghei, a rodent model for human malaria species including P. falciparum, the stability of repressed mRNAs requires the translational repressors DOZI and CITH.

Genome wide adaptations of Plasmodium falciparum in response to lumefantrine selective drug pressure.

The combination therapy of the Artemisinin-derivative Artemether (ART) with Lumefantrine (LM) (Coartem®) is an important malaria treatment regimen in many endemic countries. Resistance to Artemisinin has already been reported, and it is feared that LM resistance (LMR) could also evolve quickly. Therefore molecular markers which can be used to track Coartem® efficacy are urgently needed.

Universal features of post-transcriptional gene regulation are critical for Plasmodium zygote development.

A universal feature of metazoan sexual development is the generation of oocyte P granules that withhold certain mRNA species from translation to provide coding potential for proteins during early post-fertilization development. Stabilisation of translationally quiescent mRNA pools in female Plasmodium gametocytes depends on the RNA helicase DOZI, but the molecular machinery involved in the silencing of transcripts in these protozoans is unknown. Using affinity purification coupled with mass-spectrometric analysis we identify a messenger ribonucleoprotein (mRNP) from Plasmodium berghei gametocytes defined by DOZI and the Sm-like factor CITH (homolog of worm CAR-I and fly Trailer Hitch).

Gene copy number variation throughout the Plasmodium falciparum genome.

Background: Gene copy number variation (CNV) is responsible for several important phenotypes of the malaria parasite Plasmodium falciparum, including drug resistance, loss of infected erythrocyte cytoadherence and alteration of receptor usage for erythrocyte invasion. Despite the known effects of CNV, little is known about its extent throughout the genome.

Results: We performed a whole-genome survey of CNV genes in P.

Sir2 paralogues cooperate to regulate virulence genes and antigenic variation in Plasmodium falciparum.

Cytoadherance of Plasmodium falciparum-infected erythrocytes in the brain, organs and peripheral microvasculature is linked to morbidity and mortality associated with severe malaria. Parasite-derived P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) molecules displayed on the erythrocyte surface are responsible for cytoadherance and undergo antigenic variation in the course of an infection.

The differential regulation of Lck kinase phosphorylation sites by CD45 is critical for T cell receptor signaling responses.

The molecular mechanisms whereby the CD45 tyrosine phosphatase (PTPase) regulates T cell receptor (TCR) signaling responses remain to be elucidated. To investigate this question, we have reconstituted CD45 (encoded by Ptprc)-deficient mice, which display severe defects in thymic development, with five different expression levels of transgenic CD45RO, or with mutant PTPase null or PTPase-low CD45R0. Whereas CD45 PTPase activity was absolutely required for the reconstitution of thymic development, only 3% of wild-type CD45 activity restored T cell numbers and normal cytotoxic T cell responses.

Microarray-based comparative genomic analyses of the human malaria parasite Plasmodium falciparum using Affymetrix arrays.

Microarray-based comparative genomic hybridization (CGH) provides a powerful tool for whole genome analyses and the rapid detection of genomic variation that underlies virulence and disease. In the field of Plasmodium research, many of the parasite genomes that one might wish to study in a high throughput manner are not laboratory clones, but clinical isolates. One of the key limitations to the use of clinical samples in CGH, however, is the miniscule amounts of genomic DNA available.