Abstract:
Cellular pathways involved in cell entry by African horse sickness virus (AHSV), a member
of the Orbivirus genus within the Reoviridae family, have not yet been determined. Here, we
show that acidic pH is required for productive infection of BSR cells by AHSV-4, suggesting
that the virus is likely internalized by an endocytic pathway. We subsequently analyzed the
major endocytic routes using specific inhibitors and determined the consequences for AHSV-
4 entry into BSR cells. The results indicated that virus entry is dynamin dependent, but
clathrin- and lipid raft/caveolae-mediated endocytic pathways were not used by AHSV-4 to
enter and infect BSR cells. Instead, binding of AHSV-4 to BSR cells stimulated uptake of a
macropinocytosis-specific cargo and inhibition of Na+/H+ exchangers, actin polymerization
and cellular GTPases and kinases involved in macropinocytosis significantly inhibited
AHSV-4 infection. Altogether, the data suggest that AHSV-4 infects BSR cells by utilizing
macropinocytosis as the primary entry pathway.
