Deletion of T cells bearing the V beta8.1 T-cell receptor following mouse mammary tumor virus 7 integration confers resistance to murine cerebral malaria.
Plasmodium berghei ANKA induces a fatal neurological syndrome known as cerebral malaria (CM) in susceptible mice. Host genetic elements are among the key factors determining susceptibility or resistance to CM. Analysis of mice of the same H-2 haplotype revealed that mouse mammary tumor virus 7 (MTV-7) integration into chromosome 1 is one of the key factors associated with resistance to neurological disease during P. berghei ANKA infection. We investigated this phenomenon by infecting a series of recombinant inbred mice (CXD2), derived from BALB/c (susceptible to CM) and DBA/2 (resistant to CM) mice, with P. berghei ANKA. We observed differences in susceptibility to CM induced by this Plasmodium strain. Mice with the MTV-7 sequence in their genome were resistant to CM, whereas those without integration of this gene were susceptible. Thus, an integrated proviral open reading frame or similar genomic sequences may confer protection against neuropathogenesis during malaria, at least in mice.
Gorgette
Olivier
O
Unité d'Immunophysiopathologie Infectieuse, CNRS URA 1961, Département d'Immunologie, Institut Pasteur, 75724 Paris Cedex 15, France.
Existe
Alexandre
A
Boubou
Mariama Idrissa
MI
Bagot
Sébastien
S
Guénet
Jean-Louis
JL
Mazier
Dominique
D
Cazenave
Pierre-André
PA
Pied
Sylviane
S
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D016779:Malaria, Cerebral / Q000235:genetics* / Q000276:immunology; D008297:Male; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008817:Mice, Mutant Strains; D010962:Plasmodium berghei / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D016662:Virus Integration / Q000235:genetics* / Q000276:immunology
D016693:Receptors, Antigen, T-Cell, alpha-beta