PMID- 28371168
OWN - NLM
STAT- MEDLINE
DCOM- 20180530
LR  - 20180613
IS  - 1462-5822 (Electronic)
IS  - 1462-5814 (Linking)
VI  - 19
IP  - 9
DP  - 2017 Sep
TI  - AMA1 and MAEBL are important for Plasmodium falciparum sporozoite infection of 
      the liver.
LID - 10.1111/cmi.12745 [doi]
AB  - The malaria sporozoite injected by a mosquito migrates to the liver by traversing 
      host cells. The sporozoite also traverses hepatocytes before invading a terminal 
      hepatocyte and developing into exoerythrocytic forms. Hepatocyte infection is 
      critical for parasite development into merozoites that infect erythrocytes, and 
      the sporozoite is thus an important target for antimalarial intervention. Here, 
      we investigated two abundant sporozoite proteins of the most virulent malaria 
      parasite Plasmodium falciparum and show that they play important roles during 
      cell traversal and invasion of human hepatocytes. Incubation of P. falciparum 
      sporozoites with R1 peptide, an inhibitor of apical merozoite antigen 1 (AMA1) 
      that blocks merozoite invasion of erythrocytes, strongly reduced cell traversal 
      activity. Consistent with its inhibitory effect on merozoites, R1 peptide also 
      reduced sporozoite entry into human hepatocytes. The strong but incomplete 
      inhibition prompted us to study the AMA-like protein, merozoite apical 
      erythrocyte-binding ligand (MAEBL). MAEBL-deficient P. falciparum sporozoites 
      were severely attenuated for cell traversal activity and hepatocyte entry in 
      vitro and for liver infection in humanized chimeric liver mice. This study shows 
      that AMA1 and MAEBL are important for P. falciparum sporozoites to perform 
      typical functions necessary for infection of human hepatocytes. These two 
      proteins therefore have important roles during infection at distinct points in 
      the life cycle, including the blood, mosquito, and liver stages.
CI  - (c) 2017 John Wiley & Sons Ltd.
FAU - Yang, Annie S P
AU  - Yang ASP
AD  - The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 
      Australia.
AD  - Department of Medical Biology, The University of Melbourne, Parkville, Victoria, 
      Australia.
FAU - Lopaticki, Sash
AU  - Lopaticki S
AD  - The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 
      Australia.
FAU - O'Neill, Matthew T
AU  - O'Neill MT
AD  - The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 
      Australia.
FAU - Erickson, Sara M
AU  - Erickson SM
AD  - The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 
      Australia.
AD  - Department of Medical Biology, The University of Melbourne, Parkville, Victoria, 
      Australia.
FAU - Douglas, Donna N
AU  - Douglas DN
AD  - Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
FAU - Kneteman, Norman M
AU  - Kneteman NM
AD  - Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
FAU - Boddey, Justin A
AU  - Boddey JA
AUID- ORCID: 0000-0001-7322-2040
AD  - The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 
      Australia.
AD  - Department of Medical Biology, The University of Melbourne, Parkville, Victoria, 
      Australia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170518
PL  - India
TA  - Cell Microbiol
JT  - Cellular microbiology
JID - 100883691
RN  - 0 (Antigens, Protozoan)
RN  - 0 (MAEBL protein, Plasmodium falciparum)
RN  - 0 (Membrane Proteins)
RN  - 0 (Protozoan Proteins)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (apical membrane antigen I, Plasmodium)
SB  - IM
MH  - Animals
MH  - Anopheles/parasitology
MH  - Antigens, Protozoan/genetics
MH  - Cell Line
MH  - Disease Models, Animal
MH  - Erythrocytes/parasitology
MH  - Hepatocytes/*parasitology
MH  - Humans
MH  - Liver/parasitology
MH  - Malaria, Falciparum/*parasitology
MH  - Membrane Proteins/*antagonists & inhibitors/genetics
MH  - Merozoites/*growth & development
MH  - Mice
MH  - Mice, SCID
MH  - Plasmodium falciparum/*pathogenicity
MH  - Protozoan Proteins/*antagonists & inhibitors/genetics
MH  - Receptors, Cell Surface/*antagonists & inhibitors/genetics
MH  - Sporozoites/*growth & development
OTO - NOTNLM
OT  - cell traversal
OT  - hepatocyte
OT  - humanized mice
OT  - invasion
OT  - malaria
OT  - sporozoite
EDAT- 2017/04/04 06:00
MHDA- 2018/05/31 06:00
CRDT- 2017/04/04 06:00
PHST- 2016/11/28 00:00 [received]
PHST- 2017/03/23 00:00 [revised]
PHST- 2017/03/28 00:00 [accepted]
PHST- 2017/04/04 06:00 [pubmed]
PHST- 2018/05/31 06:00 [medline]
PHST- 2017/04/04 06:00 [entrez]
AID - 10.1111/cmi.12745 [doi]
PST - ppublish
SO  - Cell Microbiol. 2017 Sep;19(9). doi: 10.1111/cmi.12745. Epub 2017 May 18.