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→Pathogenesis
==Pathogenesis==
==Pathogenesis==
Infection is by aerosol contact or direct spread. Entrance is through skin abrasions or mucous membranes. The incubation is usually 3-4 days (but may vary to 5-10 days). Virus infects epithelial cells of tonsillar crypts and subsequently spreads to regional lymph nodes via lymphatics. It enters the blood stream, replicates in the spleen, bone marrow and lymph nodes. Multiple haemorrhages are caused by degeneration of endothelial cells of blood vessles and thrombocytopaenia resulting in poor blood coagulation. In acute CSF, pigs die from the acute angiopathy, shock and febrile response. Pigs that survive develop a chronic form of the disease with enteric and joint lesions that are the result of tissue infarction. Piglets infected ''in utero'' are born persistently infected. They grow poorly and excrete virus over long periods.
Infection is by aerosol contact or direct spread. Entrance is through skin abrasions or mucous membranes. The incubation is usually 3-4 days (but may vary to 5-10 days). Virus infects epithelial cells of tonsillar crypts and subsequently spreads to regional lymph nodes via lymphatics. It enters the blood stream, replicates in the spleen, bone marrow and lymph nodes. Multiple haemorrhages are caused by degeneration of endothelial cells of blood vessles and thrombocytopaenia resulting in poor blood coagulation. In acute CSF, pigs die from the acute angiopathy, shock and febrile response. Pigs that survive develop a chronic form of the disease with enteric and joint lesions that are the result of tissue infarction. Piglets infected ''in utero'' are born persistently infected. They grow poorly and excrete virus over long periods.
A major area of recent study has been the nature of
the interaction between virus and host and attempts to
Research in Veterinary Science 75 (2003) 169–178
www.elsevier.com/locate/rvsc
* Corresponding author. Tel.: +44-1483-231012; fax: +44-1483-
232621.
E-mail address: david.paton@bbsrc.ac.uk (D.J. Paton).
0034-5288/$ - see front matter � 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0034-5288(03)00076-6
understand how the virus is able to avoid the innate
immune system, delay the onset of acquired immunity
and produce its pathogenic effects. Like other pestiviruses,
CSFV grows readily in vitro and is able to cause a
persistent, non-cytopathic infection of cell cultures. This
indicates that the virus can avoid the antiviral effects of
type I interferon and prevent programmed cell death
(apoptosis). Indeed, porcine cells infected with CSFV
are strongly protected against stimuli that normally
trigger apoptosis, such as treatment with double-stranded
RNA, and resist the antiviral effects of type I interferon
(Ruggli et al., 2002). The first protein encoded
by the genome, Npro, is an autoprotease that cleaves
itself from the nascent viral polyprotein and whose
function has been enigmatic. Recently, it has been
shown that CSFV, lacking Npro induces rather than
inhibits an interferon response in infected monocytes
(Ruggli et al., 2002). CSFV is also immunosuppressive
and neutralising antibodies may not appear until three
weeks after infection. Since the virus is so innocuous in
vitro, it has long been suspected that the serious lesions
found in vivo must have an immunopathological origin.
During infection, there are profound changes in the
bone marrow and in the circulating white cell population
and these may precede widespread infection of these
cell types (Knoetig et al., 1999; Summerfield et al., 1998,
2001a). This suggests an indirect cytopathic effect induced
in mainly uninfected cells, damaged by a soluble
viral factor or by some other disturbance of cellular
homeostasis. There is evidence for both of these mechanisms.
Firstly, there is a soluble viral protein Erns that
at high concentrations is able to induce apoptosis in
lymphocytes in vitro (Bruschke et al., 1997). However,
supernatant fluids collected from cell cultures infected
with CSFV do not induce apoptosis (Summerfield et al.,
2001b). Secondly, virus replication in monocytes and
macrophages induces the release of cytokines including
prostaglandin-E2 and interleukin-1, which have a
probable role in fever and haemorrhages (Knoetig et al.,
1999). Although the majority of pestiviruses are noncytopathic
in vitro, BVD viruses from cases of mucosal
disease and a small minority of CSF viruses can be cytopathic
in vitro, expression of NS3 being the hallmark
of such cytopathic viruses (Kummerer et al., 2000).
==Diagnosis==
==Diagnosis==