Arch Virol (2001) 146: 1831–1840
Phorbol dibutyrate-induced megakaryocytic differentiation
increases susceptibility of K562 cells to SA11 rotavirus infection
G. M. Sanders
, M. J. Hewish, and B. S. Coulson
Department of Microbiology and Immunology,
The University of Melbourne, Victoria, Australia
Accepted April 3, 2001
Summary. The role of integrins previously implicated as rotavirus receptors in
determining cellular susceptibility to SA11 rotavirus was studied, using phorbol
dibutyrate (PDB) treatment of K562 cells to induce megakaryocytic differentia-
tion. Expression of ␣2␤1 integrin was detected after 2 days in PDB, and peaked
after PDB treatment for 4–7 days. SA11 titres were increased by 1.8- to 10.8-fold
over untreated cells after PDB treatment for 2–7 days, and correlated with levels
of ␣2␤1 integrin expression in PDB-treated K562 cells.
A crucial step in virus replication is the interaction of the virus with cell surface
receptors. For rotaviruses, the spike protein VP4 is the major cell attachment
protein, although the major outer capsid protein VP7 may play a minor role .
The simian rotavirus SA11 is the type species of the family Reoviridae, genus
Rotavirus, species Rotavirus A. The trypsin cleavage product of SA11 rotavirus
, contains the ␣2␤1 integrin ligand sequence DGE and the ␣4 ligand
sequence. SA11 VP7 contains the ␣X␤2 ligand sequence GPRP and the ␣4 ligand
sequence LDV. Peptides containing DGE and GPRP speciﬁcally blocked SA11
infectivity in MA104 cells . SA11 infectivity in MA104 and Caco-2 cells is
speciﬁcally blocked by monoclonal antibodies (mAbs) to ␣2 and ␤2 integrins
. Cellular susceptibility to SA11 correlates with levels of expression of ␣2␤1
and ␣X␤2 [4, 6]. Binding of SA11 to sialic acids on the cell surface also leads to
infection, although sialic acids are not essential for virus infectivity .
Present address: Centre for Animal Biotechnology, The University of Melbourne,
Victoria 3010, Australia.