Entry process of porcine arterivirus in macrophages and link with virulence/pathogenicity

Porcine reproductive and respiratory syndrome (PRRS) is a devastating disease in
pigs, characterized by reproductive and respiratory problems. It is caused by an
arterivirus with a specific tropism for macrophages. Recently, more virulent strains
emerged in Europe and Asia causing high mortalities. Vaccines are losing their
efficacy and in order to find an answer to this problem, better insights in virus entry
and immune response are essential. The promoter’s laboratory has already identified a
large part of the virus entry (receptors/viral ligands, importance of sialic acids on viral
ligands, role of low pH/proteases) and, based on this information, developed a new
inactivated vaccine. However, there are still several pieces of the puzzle missing.
First, the internalization mechanism is not fully understood. Sialoadhesin is the main
internalization molecule, but does not contain a known endocytic motif in its
cytoplasmic tail. Cellular co-factors are most probably involved and will be identified.
Furthermore, it will be analysed if sialoadhesin recycles to the cell surface upon
endocytosis. Second, further downwards in the entry process, it was found that
proteases are involved during virus disassembly. In the present project, this protease
and the viral ligand that is cleaved will be identified. In a last part of the project, it
will be examined why new highly virulent strains are able to infect monocytic cells
that do not carry sialoadhesin; a new receptor will be traced.