Biology Reference
In-Depth Information
animal model for studying human diseases, so the identification of pig model biomark-
ers for viral diseases is an important step towards identification of human counterparts.
The identification of biomarkers has already been proposed as a way to create new
diagnostic tools for specific microbial infection [18, 19].
Previous studies have shown the value of using cross-species hybridization [20].
Here, using the Illumina human oligonucleotide Refset in a cross-species study we
identifi ed hundreds of probes with expression levels that were altered in brain and lung
following wild type PRV infection of young piglets, which typically have more severe
clinical manifestations than the adult. In adult pigs one observes mainly, or exclusive-
ly, the respiratory symptoms, whereas in piglets and rodent hosts there is invariably in-
vasion of the CNS [21, 22]: piglets exhibit signs in the form of tremor, trembling, and
incoordination. Thus piglets permit the potential identifi cation of a wider spectrum of
genes involved in the disease processes in different tissues.
Classifi cation of the genes that are differentially expressed in piglet brain into
functional groups revealed that several genes are also implicated in human neuro-
degenerative disorders. These include genes in the pathways for amyotrophic lateral
sclerosis (
NEF3
,
NEFL
,
NEFH
), Huntington's disease (
CALM3
,
CLTC
,
CLTB
), neu-
rodegenerative disorders (
APLP1
,
NEFH
,
FBXW7
), Parkinson's disease (
GPR37
) and
prion disease (
APLP1
,
NFE2L2
). It is not known if these transcriptional changes are
primary or secondary effects of the PRV infection.
Several members of the immune response pathways (e.g., the B cell receptor
signaling pathway, the Fc epsilon RI signaling pathway, natural killer cell mediated
cytotoxicity, and the T cell receptor signaling pathway) were also transcriptionally
regulated by PRV infection in brain. This is in agreement with the results from PRV or
HSV-1 infection in primary cultures of rat embryonic fi broblasts [5]. In addition, simi-
lar changes to immune response pathway (e.g., antigen processing and presentation,
complement, and coagulation cascades), cell differentiation and metabolism pathway
genes have been described in the host following PRV infection in rat CNS [6]. Our
experiment not only identifi ed pathways, but also several genes in common with these
previous studies:
FOS
and
LCP2
, both involved in T cell receptor signaling pathways;
the
TGFβ
signal transduction pathway components
ID4
and
THBS4
, highlighted in
the study of PRV infection of primary cultures of rat embryonic fi broblasts [5, 6];
and
SERPINE-1
, identifi ed in both earlier rat studies. These genes may be potential
diagnostic and therapeutic targets for viral encephalitis and other neurodegenerative
or neuroinfl ammatory diseases.
Several genes of the TGFβ pathway were also identifi ed here in the infected lung
tissue (e.g.,
PPP2CA
,
PPP2CB
,
ID2
,
ID3
, and
ID4
). After PRV infection, most older
swine exhibit signs of respiratory disease, and the study of the lung is therefore im-
portant for understanding what genes may be involved in the disease process. We
identifi ed 1,130 differentially expressed probes as a result of wild-type PRV infection;
this is fi ve times higher than in the brain. The lung may be more transcriptionally ac-
tive, or have a more pronounced immune response that might involve more immune
cell types than the brain. In addition, we have identifi ed fi ve possible viral receptors,
normally necessary for the spread of virus between cells, up-regulated in the infected
