Effect of infection with the ts22 mutant of Semliki Forest virus on development of the central nervous system in the fetal mouse

Abstract

The A7 strain of Semliki Forest virus induces rapid fetal death in pregnant mice, whereas the ts22 mutant derived from it is teratogenic for a proportion of fetuses. Both A7 and ts22 induce viremia and infect the central nervous systems and fetuses of pregnant mice. Using immunogold-silver staining, a cDNA probe for a Semliki Forest virus nonstructural sequence, and a riboprobe derived from the same sequence, we showed that the skin and musculoskeletal systems of fetuses from mothers infected with ts22 were often heavily infected but the central nervous systems were not labeled before day 17 of pregnancy. Damage to the neural tube, including open-neural-tube defects, was detected in fetuses following infection of the mother at days 8 and 10 of pregnancy with both A7 and ts22. For ts22, neural tube damage induced by fetal infection before day 17 of pregnancy appeared to be indirect and caused by virus infection of mesenchymal cells surrounding the developing neural tube.

The alphaviruses: gene expression, replication, and evolution.

“…Attenuated variants of SF have been isolated, and the pathology of virus infection has been studied (13,320,321). Although no details of the molecular changes involved are known, several interesting studies on the pathologic changes caused by an attenuated variant of SF, called A7(74), have been reported.…”

The molecular pathogenesis of Semliki Forest virus: a model virus made useful?

“…Teratogenic effects induced by SFV include skeletal, skin and neural tube defects. They probably result in all cases from infection of undifferentiated mesenchymal cells (Mabruk et al ., 1988 , 1989 ). The mechanism of teratogenesis by SFV and other viruses has been reviewed by Atkins et al .…”

Analysis of the molecular basis of neuropathogenesis of RNA viruses in experimental animals: relevance for human disease?

“…ts22 induces open neural tube defects in a minority of infected fetuses: the majority of fetuses show abnormal development of the neuroepithelium. These neural tube defects are indirectly induced by infection of mesenchy-ma1 cells adjacent to the neural tube, and not by infection of the neuroepithelium itself [44].…”