Journal of Experimental Medicine, Vol 157, 1028-1039, Copyright © 1983 by Rockefeller University Press
Induction of acute thrombocytopenia and infection of megakaryocytes by Rauscher murine leukemia virus reflect the genetic susceptibility to leukemogenesis
GE Grau, P Puthavathana, S Izui and PH Lambert
Acute thrombocytopenia and megakaryocyte infection have been investigated
during the preleukemic phase of the disease induced by the Rauscher murine
leukemia virus (RMuLV) in mice. Injection of RMuLV, either intravenously or
intraperitoneally, rapidly induced thrombocytopenia, possibly as a result
of direct interaction between platelets and viral particles. The
susceptibility to this acute thrombocytopenia was genetically controlled
and was inherited as a dominant trait. Murine strains with H-2d or H-2k
haplotype, which are susceptible to the induction of leukemia by RMuLV,
developed thrombocytopenia, whereas leukemia-resistant H-2b and H-2q
strains of mice failed to develop thrombocytopenia. Using B10 H-2-congenic
and intra-H-2-recombinant mice, it was shown that the susceptibility to
RMuLV-induced thrombocytopenia was controlled by gene(s) in or closely
linked to the D region of the H-2 complex. Megakaryocytes may be one of the
first sites for the replication of RMuLV. Indeed, among bone marrow cells,
only megakaryocytes expressed viral antigens gp70 and p30 during the
initial phase of RMuLV infection. In addition, megakaryocytes from infected
mice were able to transfer preleukemic thrombocytopenia as well as leukemia
in syngeneic mice. The infection of megakaryocytes by RMuLV appears to be
genetically controlled in a manner similar to the induction of
thrombocytopenia, since only the megakaryocytes from mice developing
thrombocytopenia were infected by RMuLV. These results indicate that the
gene(s) governing the induction of thrombocytopenia by RMuLV may be the
same gene(s) (or closely linked to the gene) that controls the
susceptibility to leukemogenesis, and would be consistent with the
expression of the gene product, presumably a receptor-like molecule for
RMuLV, on platelet and megakaryocyte membranes.
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