Poster Presentation First Malaria World Congress 2018

Co-expression of variant surface antigens in Rosetting of Plasmodium falciparum  (#395)

Digjaya Utama 1 2 , Somya Mehra 1 2 , Zahra Razook 1 , Christelle Buffet 3 , Stephen Rogerson 3 , Jarrod Sandow 4 , Andrew Webb 4 , Alyssa Barry 1 2
  1. Division of Population Health and Immunity, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
  2. Medical Biology, University of Melbourne, Carlton, VIC, Australia
  3. Department of Medicine, Melbourne University, Peter Doherty Institute, Melbourne, VIC, Australia
  4. Division of Systems Biology & Personalised Medicine, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia

One of the mechanisms leading to severe malaria due to Plasmodium falciparum infection is rosetting, where infected erythrocytes (IEs) adhere to non-infected erythrocytes. These mechanisms are mediated by parasite variant surface antigens (VSAs) and host receptors on erythrocytes. At least three VSAs are known to mediate resetting: P. falciparum Erythrocyte Membrane Protein-1 (PfEMP1), Repeat Interspersed Family protein (RIFIN), and Subtelomeric Variant Open Reading Frame (STEVOR), encoded by multifamily var, rif, and stevor genes, respectively. This study investigates the potential co-expression network of VSAs in rosetting P. falciparum parasites using transcriptomic and proteomic approaches. The RNA and IE membrane proteins were extracted from rosetting and non-rosetting P. falciparum lines of the BB12 strain for RNA sequencing (Illumina) and mass spectrometry, respectively. Considering the hypervariable nature of the genes encoding VSAs, we first generated a reference genome by short-read (Illumina) and long-read (Oxford Nanopore) whole genome sequencing, followed by hybrid de novo assembly using Canu and Pilon. The RNAseq data showed significant upregulation of a subset of group-A var and rif, but not stevor genes in the rosetting parasites. Proteomic data is currently being analysed and will be presented. By using a multi-omics strategy, this study will provide better insight into the roles of VSAs in rosetting which can help to guide the development of interventions to reduce the burden of severe P. falciparum malaria.