Immunomodification and the Expression of Virulence in Mice by Defined Strains of Semliki Forest Virus: the Effects of Cyclophosphamide

Abstract

SUMMARYMice were infected i.c. or i.p. by an avirulent clone of Semliki Forest virus at various times before or after the i.p. administration of a single dose of cyclophosphamide. Consequent changes in the patterns of viraemia and antibody production are interpreted in terms of the potentiation of the initial infection or the decreased resistance to subsequent lethal challenge.These changes demonstrate two distinct modes of immunomodification determined by the time of cyclophosphamide administration in relation to virus infection, but not correlated with the death or protection of individual mice.These results are discussed in relation to the early regulatory functions of T and B cells which may influence the expression of virulence but escape conventional assay during the critical first 3 days following infection.

Immunomodification and the Expression of Virulence in Mice by Defined Strains of Semliki Forest Virus: the Effects of Myocrisin and l-Asparaginase

“…These were as in the previous paper (Bradish et al 1975) and earlier reports (Bradish, Allner & Maber, 1971). Most experiments were with the avirulent strain A7.CI or its derived clone A7(74).CI which efficiently immunize young mature mice (~ IOO p.f.u./i.p.…”

“…A differentially greater sensitivity of T cells than B cells to the action of 1-asparaginase has been reported by Berenbaum,Cope & Jeffrey (I973). If, as these authors suggest, B cells enjoy a partially protective micro-environment, then this is evidently less effective against the action of cyclophosphamide which (Table 4 and Bradish et al 1975) influences antibody memory and the development of protection against challenge (secondary potentiation) to an extent not observed with 1-asparaginase.…”

“…More direct tests within the first 4 days of the properties of' early' serum in passive protection or of'early' cells in adoptive immunity encounter the difficulties of detection already discussed (Bradish & Allner, 1972;Bradish et al 1975).…”

Aurothiolates enhance the replication of Semliki Forest virus in the CNS and the exocrine pancreas

“…Aurothiolates are linear, 2-coordinate complexes in which two ligands are covalently bound on either side of a gold nucleus in a +1 oxidation state (gold (I)). Early studies suggested these gold compound affected the outcome of SFV infection by an effect on macrophages (Allner et al, 1974;Bradish et al, 1975). Subsequent studies con®rmed that these compound have an effect on macrophages Webb, 1982, 1990) but suggested that this was not the basis for their effect on the course of SFV infection (Mehta and Webb, 1987;.…”

“…It has been demonstrated that treatment of 3 ± 4-week-old mice with the gold compound sodium aurothiomalate (GSTM) prior to inoculation with A7(74) renders this infection lethal (Allner et al, 1974;Bradish et al, 1975;Pathak and Webb, 1983;Mehta and Webb, 1982, Gates et al, 1984Mehta et al, 1987. GSTM is an aurothiolate compound which has been used in the treatment of rheumatoid arthritis.…”