Issue |
Vet. Res.
Volume 31, Number 1, January-February 2000
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|
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Page(s) | 22 - 22 | |
DOI | https://doi.org/10.1051/vetres:2000035 | |
How to cite this article | Vet. Res. (2000) 22-22 |
PRRSV-macrophage interaction and putative receptors
H. Nauwynck, X. Duan and M. PensaertLaboratory of Virology, Faculty of Veterinary Medicine, University of Gent, Salisburylaan 133, 9820 Merelbeke, Belgium
Abstract -
Porcine reproductive and respiratory syndrome virus (PRRSV),
a member of the Arteriviridae family, has a restricted cell tropism
in its host, the pig. Mainly cells of the monocyte/macrophage
(mø)
lineage are susceptible, which are situated in different locations
such as the tonsils, lungs, lymph nodes and spleen. The observation
that several subpopulations of this cell lineage do not permit a
complete replication is important. Blood monocytes, peritoneal
macrophages and progenitor cells in the bone marrow are examples
of refractory mø. The basis for the restricted replication of
PRRSV in certain cell types can be found in the different subsequent
steps which have to be gone through successfully before a new virus
is produced: attachment, entry, release of the genome, transcription,
translation and assembly. The inhibition of one of these steps will
result in a non-permissive status of the cell. The early events of the
replication cycle have already been studied extensively and will be discussed.
The entry of PRRSV starts with attachment. Binding of PRRSV to alveolar
macrophages happens in a dose dependent way and is completed within one
hour at
.
The number of binding sites on the surface of a single
macrophage is quite variable but exceeds
104 per cell. Recently, two
monoclonal antibodies were produced which are able to partially block
virus attachment to the plasma membrane and to inhibit infection.
They recognise a 210 kDa protein. Since a clear colocalisation exists
between attached virus and aggregates of this protein on the plasma
membrane, it was concluded that these monoclonal antibodies either
specifically recognise the PRRSV receptor or a protein which is in close
contact with it. The fact that all PRRSV-positive cells in lungs and lymphoid
tissues carry this 210 kDa protein gives further evidence that monoclonal antibodies
are directed against a putative receptor. Further research is currently underway
to provide definitive proof that the 210 kDa protein corresponds to the PRRSV
receptor. The next step in the entry-process is the endocytosis of PRRSV. This
has been visualised by confocal microscopy using labelled virus. Within one hour,
bound virus is taken up by the cell. Since a clear colocalisation exists between
the virus and clathrin during engulfment, it can be concluded that clathrin is
involved. The fact that colocalisation is no longer present once the virus is
internalised provides evidence that clathrin is released from the membrane of
the endosomes during the movement of the virus-containing endosome inside the
cell. This finding is in agreement with the knowledge that clathrin is recycled
during clathrin-dependent, receptor-mediated endocytosis processes. Although
attachment and endocytosis of PRRSV is observed in almost all alveolar
macrophages, viral antigens are only produced in 30% of these cells. This
discrepancy suggests that one of the next steps in the replication cycle,
which is the release of the viral genome in the cytoplasm or translation,
is blocked in one way or another. How the viral genome gets free from its
envelope and arrives in the cytoplasm for transcription and translation
has not yet been clarified. It has, however, already been shown by the use
of the acidotropic agents, NH
4Cl and chloroquine, that a low pH phase is
essential during this period. It is now believed, in relation to the
knowledge of other viruses, which need a low pH-phase during early replication,
that acidification causes conformational changes in envelope glycoproteins and/or
capsid structures and triggers membrane fusion. In conclusion, it can be stated
that during the early stages of PRRSV-replication, a complex cascade of events takes
place and that the non-permissive status of a cell may be caused by a block at the
level of one of these events.
Corresponding author: H. Nauwynck Tel.: (32) 9 264 73 66; fax: (32) 9 264 73 73;
e-mail: hans.nauwynck@rug.ac.be
© INRA, EDP Sciences 2000