Unravelling malaria latency: parasite intrinsic and environmental factors influencing dormant liver stages

No master regulatory transcription factor of hypnozoites has been identified so far, suggesting that a combination of epigenetic, post-translational, and post-transcriptional regulation is controlling parasite dormancy.Environmental factors, such as temperature and vector availability, seem to be sensed by the parasite and influence relapse frequency.Host characteristics may play a role in establishing dormancy and reactivation with factors such as coinfection, host immune response, and the cellular state of hepatocytes could be sensed by the parasite. Hypnozoites – dormant Plasmodium parasites in the liver – can cause relapse infections and form a major obstacle to malaria eradication. The mechanisms controlling dormancy remain poorly understood, but hypnozoite formation and reactivation is likely regulated by a combination of parasite intrinsic factors and external stimuli. We reviewed current knowledge of Plasmodium dormancy and drew parallels with dormancy in other parasites and life-cycle stages. Epigenetic, post-transcriptional, or post-translational regulation probably jointly control hypnozoite dormancy at the intrinsic level. Additionally, environmental factors, such as vector availability, host wellbeing, and tissue microenvironment, could be instrumental to hypnozoite reactivation. A better understanding of how external stimuli influence the intrinsic reactivation switch at a mechanistic level will be required to expand the limited toolset to combat relapsing malaria. Hypnozoites – dormant Plasmodium parasites in the liver – can cause relapse infections and form a major obstacle to malaria eradication. The mechanisms controlling dormancy remain poorly understood, but hypnozoite formation and reactivation is likely regulated by a combination of parasite intrinsic factors and external stimuli. We reviewed current knowledge of Plasmodium dormancy and drew parallels with dormancy in other parasites and life-cycle stages. Epigenetic, post-transcriptional, or post-translational regulation probably jointly control hypnozoite dormancy at the intrinsic level. Additionally, environmental factors, such as vector availability, host wellbeing, and tissue microenvironment, could be instrumental to hypnozoite reactivation. A better understanding of how external stimuli influence the intrinsic reactivation switch at a mechanistic level will be required to expand the limited toolset to combat relapsing malaria.