Tolerance

In the pestivirus group, transplacental infections of the fetus can cause congenital disease and induction of immunological unresponsiveness to the virus in the fetus. In the ruminant pestiviruses (BVDV, BD), there are two virus biotypes - cytopathic and noncy-topathic. This difference correlates with distinct differences in viral polypeptides between the two biotypes. In the first 3 months of pregnancy BVDV infection of pregnant cattle with the noncytopathic BVDV virus may result either in fetal death or, as is more common, the birth of apparently normal animals which are virus positive but antibody negative. The same applies to BD infection of sheep. If infection occurs early in pregnancy during the develop ment of the immune repertoire, virus antigen is seen as self and animals become immunologically tolerant to the virus following in utera infection. These virus-positive, antibody-negative animals represent an important reservoir of infectious virus. On infection of these tolerant animals with the more virulent cyto-pathic virus, a fulminating infection results and animals die from a mucosal disease syndrome associated with destruction of the gut epithelium, inflammatory lesions of the alimentary tract and depletion of lymphoid tissue in the Peyer's patches.

Pestivirus infection in ruminants has analogies with rubella in humans. Congenital infection of the fetus with rubella is a chronic nonlytic infection associated with little inflammation but severe multisystem congenital abnormalities; 80% of congeni-tally infected children shed the virus and can secrete virus for up to 20 months after birth. The mechanism of rubella teratogenesis is unknown; nor has it been established how rubella escapes immune elimination in these children. It is possible that this could arise either because of some impairment in the capacity to make high titer antirubella immunoglobulin G (IgG) perhaps through T cell tolerance. The presence of antibodies (either host or maternal) may also exacerbate the disease and cause immune-mediated damage. The latter is not seen in the congenital pestivirus infections in ruminants as there is no transplacental passage of antibody during fetal life. The ruminant pestiviruses provide a valuable animal model for congenital rubella as well as being challenging diseases of veterinary importance.

See also: Filoviruses (Marburg virus and Ebola virus) infection and immunity; Viruses, immunity to.

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