dual scRNA-seq analysis of P. vivax infected hepatocytes

Malaria-causing <em>Plasmodium vivax</em> parasites can linger in the human liver for weeks to years, and then reactivate to cause recurrent blood-stage infection. While an important target for malaria eradication, little is known about the molecular features of the replicative and non-replicative states of intracellular <em>P. vivax</em> parasites, or their human host-cell dependencies and the host responses to them. Here, we leverage a bioengineered human microliver platform to culture patient-derived <em>P. vivax</em> parasites in primary human hepatocytes and conduct transcriptional profiling. By coupling enrichment strategies with bulk and single-cell analyses, we captured both parasite and host transcripts in individual hepatocytes throughout the infection course. We define host- and state-dependent transcriptional signatures and identify previously unappreciated populations of replicative and non-replicative parasites, sharing features with sexual transmissive forms. We find that infection suppresses transcription of key hepatocyte function genes, and that <em>P. vivax</em> elicits an innate immune response that can be manipulated to control infection. Our work provides an extendible framework and resource for understanding host-parasite interactions and reveals new insights into the biology of <em>P. vivax</em> dormancy and transmission.