Sporozoite Route of Infection Influences In Vitro var Gene Transcription of Plasmodium falciparum Parasites From Controlled Human Infections.
Antigenic variation in Plasmodium falciparum is mediated by the multicopy var gene family. Each parasite possesses about 60 var genes, and switching between active var loci results in antigenic variation. In the current study, the effect of mosquito and host passage on in vitro var gene transcription was investigated.



Thirty malaria-naive individuals were inoculated by intradermal or intravenous injection with cryopreserved, isogenic NF54 P. falciparum sporozoites (PfSPZ) generated from 1 premosquito culture. Microscopic parasitemia developed in 22 individuals, and 21 in vitro cultures were established. The var gene transcript levels were determined in early and late postpatient cultures and in the premosquito culture.



At the early time point, all cultures preferentially transcribed 8 subtelomeric var genes. Intradermal infections had higher var gene transcript levels than intravenous infections and a significantly longer intrahost replication time (P = .03). At the late time point, 9 subtelomeric and 8 central var genes were transcribed at the same levels in almost all cultures. Premosquito and late postpatient cultures transcribed the same subtelomeric and central var genes, except for var2csa



The duration of intrahost replication influences in vitro var gene transcript patterns. Differences between premosquito and postpatient cultures decrease with prolonged in vitro growth.
Institute of Tropical Medicine University of Tübingen and German Center for Infection Research, Partner Site Tübingen.
Sandra
S
Dimonte
Institute of Tropical Medicine University of Tübingen and German Center for Infection Research, Partner Site Tübingen.
Ellen I
EI
Bruske
Institute of Tropical Medicine University of Tübingen and German Center for Infection Research, Partner Site Tübingen.
Johanna
J
Hass
Institute of Tropical Medicine University of Tübingen and German Center for Infection Research, Partner Site Tübingen.
Christian
C
Supan
Institute of Tropical Medicine University of Tübingen and German Center for Infection Research, Partner Site Tübingen.
Carmen L
CL
Salazar
Institute of Tropical Medicine University of Tübingen and German Center for Infection Research, Partner Site Tübingen.
Jana
J
Held
Institute of Tropical Medicine University of Tübingen and German Center for Infection Research, Partner Site Tübingen.
Serena
S
Tschan
Institute of Tropical Medicine University of Tübingen and German Center for Infection Research, Partner Site Tübingen.
Meral
M
Esen
Max Planck Institute for Developmental Biology, Tübingen.
Matthias
M
Flötenmeyer
Max Planck Institute for Developmental Biology, Tübingen.
Iris
I
Koch
Max Planck Institute for Developmental Biology, Tübingen.
Jürgen
J
Berger
Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
Anna
A
Bachmann
Sanaria Inc, Rockville, Maryland.
Betty K L
BK
Sim
Sanaria Inc, Rockville, Maryland.
Stephen L
SL
Hoffman
Institute of Tropical Medicine University of Tübingen and German Center for Infection Research, Partner Site Tübingen Centre de Recherches Médicales de Lambaréné (CERMEL), Fondation Internationale de l'Hôpital Albert Schweitzer, Lambaréné, Gabon.
Peter G
PG
Kremsner
Institute of Tropical Medicine University of Tübingen and German Center for Infection Research, Partner Site Tübingen.
Benjamin
B
Mordmüller
Institute of Tropical Medicine University of Tübingen and German Center for Infection Research, Partner Site Tübingen.
Matthias
M
Frank
D000293:Adolescent; D000328:Adult; D000818:Animals; D000940:Antigenic Variation; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology*; D008297:Male; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000235:genetics* / Q000276:immunology*; D015800:Protozoan Proteins / Q000096:biosynthesis*; D034101:Sporozoites / Q000276:immunology*; D013997:Time Factors; D014158:Transcription, Genetic; D055815:Young Adult
D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum
Plasmodium falciparum; controlled human malaria infections; epigenetics; malaria; transcription; var genes