A Humanized Mouse Model for Plasmodium vivax to Test Interventions that Block Liver Stage to Blood Stage Transition and Blood Stage Infection

Schäfer, Carola; Roobsoong, Wanlapa; Kangwanrangsan, Niwat; Bardelli, Martino; Rawlinson, Thomas A.; Dambrauskas, Nicholas; Trakhimets, Olesya; Parthiban, Chaitra; Goswami, Debashree; Reynolds, Laura M.; Kennedy, Spencer Y.; Flannery, Erika L.; Murphy, Sean C.; Sather, D. Noah; Draper, Simon J.; Sattabongkot, Jetsumon; Mikolajczak, Sebastian A.; Kappe, Stefan H. I.

doi:10.1016/j.isci.2020.101381

Cited by 41 publications

(44 citation statements)

References 42 publications

(46 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The lack of a more efficient enucleation (Menon and Ghaffari, 2021) can be overcome by genetic complementation (Scully et al, 2019). Humanized mouse models, such as the human liver-chimeric FRG KO huHep to recapitulate the liver, and blood-stage cycles of P. vivax (Mikolajczak et al, 2015;Schäfer et al, 2020) are readily available, although at a high cost and low efficiency in terms of blood-stage breakthrough; the liver stage in vitro systems (Roth et al, 2018) are currently being optimized to unravel the mechanism of hypnozoite production, though again at a high cost. Furthermore, non-human primate monkey models, such as Aotus, Saimiri, and Rhesus, are also a possibility to study this parasite in vivo (Shaw-Saliba et al, 2016;Pasini and Kocken, 2021), although rising ethics concerns makes this model only available to certain facilities.…”

Section: Introductionmentioning

confidence: 99%

Home Sweet Home: Plasmodium vivax-Infected Reticulocytes—The Younger the Better?

Thomson-Luque

Bautista

2021

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

After a century of constant failure to produce an in vitro culture of the most widespread human malaria parasite Plasmodium vivax, recent advances have highlighted the difficulties to provide this parasite with a healthy host cell to invade, develop, and multiply under in vitro conditions. The actual level of understanding of the heterogeneous populations of cells—framed under the name ‘reticulocytes’—and, importantly, their adequate in vitro progression from very immature reticulocytes to normocytes (mature erythrocytes) is far from complete. The volatility of its individual stability may suggest the reticulocyte as a delusory cell, particularly to be used for stable culture purposes. Yet, the recent relevance gained by a specific subset of highly immature reticulocytes has brought some hope. Very immature reticulocytes are characterized by a peculiar membrane harboring a plethora of molecules potentially involved in P. vivax invasion and by an intracellular complexity dynamically changing upon its quick maturation into normocytes. We analyze the potentialities offered by this youngest reticulocyte subsets as an ideal in vitro host cell for P. vivax.

show abstract

Section: Introductionmentioning

confidence: 99%

Home Sweet Home: Plasmodium vivax-Infected Reticulocytes—The Younger the Better?

Thomson-Luque

Bautista

2021

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

show abstract

“…Expression of PVS16 , a downstream target of AP2-G increased from day 2, and onwards ( Figure 2E ). PVS16 protein has been detected in a fraction of P. vivax hepatic schizonts at day 8 (Roth et al, 2018; Schafer et al, 2020). Altogether, the data indicates that commitment to gametocytogenesis might occur early during liver-stage development in a subset of parasites, likely leading to formation of sexually committed merozoites.…”

Section: Resultsmentioning

confidence: 99%

Gene signatures and host-parasite interactions revealed by dual single-cell profiling of Plasmodium vivax liver infection

Mâncio-Silva

Gural

Wadsworth

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Malaria-causing P. vivax 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 P. vivax parasites, or the human host-cell responses to them. Here, we leverage a bioengineered human microliver platform to culture Thai clinical isolates of P. vivax in primary human hepatocytes and conduct transcriptional profiling of infected cultures. 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 defined host- and state-dependent transcriptional signatures and identified previously unappreciated populations of replicative and non-replicative parasites, sharing features with sexual transmissive forms. We found that infection suppresses transcription of key hepatocyte function genes, and that P. vivax 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 malaria dormancy and transmission.

show abstract

“…Along these lines, co-infection of EBV with Plasmodium falciparum or at least exposure to parasitic antigens and immune modulators might be explored. For the blood stage of malaria, however, the human erythrocyte reconstitution needs to be improved, while some features of the liver infection stage have been recently modeled in human hepatocyte-reconstituted mice [ 145 , 146 , 147 ]. Thus, due to the ubiquitous nature of persistent EBV infection, many molecular components have been identified that seem to be required for the immune control.…”

Section: Discussionmentioning

confidence: 99%

Roles of Lytic Viral Replication and Co-Infections in the Oncogenesis and Immune Control of the Epstein–Barr Virus

Deng

Münz

2021

Cancers

View full text Add to dashboard Cite

Epstein–Barr virus (EBV) is the prototypic human tumor virus whose continuous lifelong immune control is required to prevent lymphomagenesis in the more than 90% of the human adult population that are healthy carriers of the virus. Here, we review recent evidence that this immune control has not only to target latent oncogenes, but also lytic replication of EBV. Furthermore, genetic variations identify the molecular machinery of cytotoxic lymphocytes as essential for this immune control and recent studies in mice with reconstituted human immune system components (humanized mice) have begun to provide insights into the mechanistic role of these molecules during EBV infection. Finally, EBV often does not act in isolation to cause disease. Some of EBV infection-modulating co-infections, including human immunodeficiency virus (HIV) and Kaposi sarcoma-associated herpesvirus (KSHV), have been modeled in humanized mice. These preclinical in vivo models for EBV infection, lymphomagenesis, and cell-mediated immune control do not only promise a better understanding of the biology of this human tumor virus, but also the possibility to explore vaccine candidates against it.

show abstract

A Humanized Mouse Model for Plasmodium vivax to Test Interventions that Block Liver Stage to Blood Stage Transition and Blood Stage Infection

Cited by 41 publications

References 42 publications

Home Sweet Home: Plasmodium vivax-Infected Reticulocytes—The Younger the Better?

Home Sweet Home: Plasmodium vivax-Infected Reticulocytes—The Younger the Better?

Gene signatures and host-parasite interactions revealed by dual single-cell profiling of Plasmodium vivax liver infection

Roles of Lytic Viral Replication and Co-Infections in the Oncogenesis and Immune Control of the Epstein–Barr Virus

Contact Info

Product

Resources

About