Publication Date:
2015-11-28
Description:
The invasion of a suitable host hepatocyte by mosquito-transmitted Plasmodium sporozoites is an essential early step in successful malaria parasite infection. Yet precisely how sporozoites target their host cell and facilitate productive infection remains largely unknown. We found that the hepatocyte EphA2 receptor was critical for establishing a permissive intracellular replication compartment, the parasitophorous vacuole. Sporozoites productively infected hepatocytes with high EphA2 expression, and the deletion of EphA2 protected mice from liver infection. Lack of host EphA2 phenocopied the lack of the sporozoite proteins P52 and P36. Our data suggest that P36 engages EphA2, which is likely to be a key step in establishing the permissive replication compartment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaushansky, Alexis -- Douglass, Alyse N -- Arang, Nadia -- Vigdorovich, Vladimir -- Dambrauskas, Nicholas -- Kain, Heather S -- Austin, Laura S -- Sather, D Noah -- Kappe, Stefan H I -- 1K99AI111785-01A1/AI/NIAID NIH HHS/ -- 1R01GM101183-01A1/GM/NIGMS NIH HHS/ -- K99 AI111785/AI/NIAID NIH HHS/ -- R01 GM101183/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Nov 27;350(6264):1089-92. doi: 10.1126/science.aad3318.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Infectious Disease Research (formerly Seattle Biomedical Research Institute), 307 Westlake Avenue North, No. 500, Seattle, WA 98109, USA. alexis.kaushansky@cidresearch.org stefan.kappe@cidresearch.org. ; Center for Infectious Disease Research (formerly Seattle Biomedical Research Institute), 307 Westlake Avenue North, No. 500, Seattle, WA 98109, USA. ; Center for Infectious Disease Research (formerly Seattle Biomedical Research Institute), 307 Westlake Avenue North, No. 500, Seattle, WA 98109, USA. Department of Global Health, University of Washington, Seattle, WA 98195, USA. ; Center for Infectious Disease Research (formerly Seattle Biomedical Research Institute), 307 Westlake Avenue North, No. 500, Seattle, WA 98109, USA. Department of Global Health, University of Washington, Seattle, WA 98195, USA. alexis.kaushansky@cidresearch.org stefan.kappe@cidresearch.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26612952" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Anopheles/parasitology
;
Cell Line, Tumor
;
Hepatocytes/*enzymology/*parasitology
;
Humans
;
Malaria/*enzymology/genetics/*parasitology
;
Mice
;
Mice, Inbred BALB C
;
Mice, Mutant Strains
;
Plasmodium/genetics/*physiology
;
Protozoan Proteins/*metabolism
;
Receptor, EphA2/genetics/*metabolism
;
Sporozoites/*physiology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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