Functional genomics of simian malaria parasites and host-parasite interactions.

Mary R Galinski

doi:10.1093/bfgp/elz013

Abstract

Two simian malaria parasite species, Plasmodium knowlesi and Plasmodium cynomolgi, cause zoonotic infections in Southeast Asia, and they have therefore gained recognition among scientists and public health officials. Notwithstanding, these species and others including Plasmodium coatneyi have served for decades as sources of knowledge on the biology, genetics and evolution of Plasmodium, and the diverse ramifications and outcomes of malaria in their monkey hosts. Experimental analysis of these species can help to fill gaps in knowledge beyond what may be possible studying the human malaria parasites or rodent parasite species. The genome sequences for these simian malaria parasite species were reported during the last decade, and functional genomics research has since been pursued. Here research on the functional genomics analysis involving these species is summarized and their importance is stressed, particularly for understanding host–parasite interactions, and potentially testing novel interventions. Importantly, while Plasmodium falciparum and Plasmodium vivax can be studied in small New World monkeys, the simian malaria parasites can be studied more effectively in the larger Old World monkey macaque hosts, which are more closely related to humans. In addition to ex vivo analyses, experimental scenarios can include passage through Anopheline mosquito hosts and longitudinal infections in monkeys to study acute and chronic infections, as well as relapses, all in the context of the in vivo host environment. Such experiments provide opportunities for understanding functional genomic elements that govern host–parasite interactions, immunity and pathogenesis in-depth, addressing hypotheses not possible from in vitro cultures or cross-sectional clinical studies with humans.

Highlights

Human infections with simian malaria parasites have been confirmed in Southeast Asia, given the availability and strategic use of genomic technologies [1–3]
While their numbers remain relatively small compared to the hundreds of millions of human cases of malaria caused annually by Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale and Plasmodium malariae [4], the zoonotic cases can cause illness and morbidity, there have been cases of death caused by Plasmodium knowlesi malaria [5–8], and the possibility of severe illness caused by Plasmodium cynomolgi
Plasmodium knowlesi was identified as a zoonotic species of public health importance in 2004 in Malaysia based on using polymerase chain reaction (PCR) amplification methods and gene sequence analysis, and it has since been noted as the main cause of malaria in areas of Malaysia and a threat in many neighboring countries [1, 7, 13, 14]

Summary

Introduction

Human infections with simian malaria parasites have been confirmed in Southeast Asia, given the availability and strategic use of genomic technologies [1–3]. With the normal production of all insect stages of the parasite including infectious sporozoites and liverstage forms in culture, functional genomics investigations based on the full life cycle of this species will be more accessible, and together with the strategic use of in vivo models, the prospects will be strengthened for identifying novel liverstage targets for future interventions against P. vivax Both species, P. cynomolgi and P. vivax, harbor dormant parasite forms in the liver called hypnozoites [126–129] that can become activated weeks or months after a primary blood-stage infection and cause relapsing episodes of malaria. Going forward, generating comparable clones and studies with P. coatneyi may prove to be useful; regardless, there is great potential for functional genomics advances with P. coatneyi, building upon extensive knowledge gained from the variety of in vivo NHP infection experiments detailed above

Concluding remarks

Key Points