Characterization of Interferon Induction in Mice of Resistant and Susceptible Strains during Murine Cytomegalovirus Infection

Abstract

SUMMARYComparison of the induction of plasma interferon (IFN) by murine eytomegalovirus (MCMV) in BALB/c and CBA mice demonstrated similar kinetics of induction with maximum titres at 6 and 48 h after infection. Although neutralized by antibody to type I (~ and fi) IFN, the IFN was predominantly acidqabile. The 6 h titre was markedly dependent upon the dose and method of preparation of MCMV and also the strain of mouse used. Higher plasma IFN titres were found in CBA than in BALB/c mice tbllowing both intraperitoneal or intravenous infection but this strain variation was not apparent in IFN levels in the spleen and liver. IFN induced by MCMV in CBA and BALB/c mice was equally effective at inhibiting MCMV replication in vitro. Cultured embryo fibroblasts derived from CBA and BALB/c mice produced similar levels of IFN, but it was not detected until 24 h after infection. Use of irradiation chimeras prepared from H-2-compatible high IFN producers (CBA) and low producers (B10.BR) showed that the level of IFN produced at 6 h was dependent upon bone marrow-derived cells.

Effect of host genotype in determining the relative roles of natural killer cells and T cells in mediating protection against murine cytomegalovirus infection

“…In both the highly resistant CBA/CaH, and moderately resistant C57BL/10 mouse strains, in vivo depletion of T cells did not affect the replication of MCMV in either the spleen or liver. The replication of MCMV within the visceral organs of CBA/CaH mice is thought to be controlled before the T cell response is fully activated, by mechanisms such as the level of susceptibility of individual target cells to infection by MCMV (Price et al, 1987(Price et al, , 1990; the production of IFN-~/fl (Allan & Shellam, 1985) and the action of NK cells . Similarly, studies using either NK cell deficient C57BL/6 beige mice (Shellam et al,198I), or C57BL/6J mice selectively depleted of NK cells (Bukowski et al, 1983;Scalzo et al, 1992;Shanley, i990;Welsh el al., 1990), have demonstrated that NK cells are primarily responsible for the control of MCMV replication in the spleens and livers of C57BL/6J mice during the early stages of infection.…”

“…Previous studies have shown that the re[aLive importance of natural killer (NK) cell activity, interferon (IFN) production and virusspecific T cell responses in the control of MCMV infection correlate with genotype in certain cases. Thus, in the resistant CBA/CaH and moderately resistant C57BL/6J and C57BL/I0 strains early protective mechanisms such as IFN production [Allan & Shellam, 1985;Grundy (Chalmer) et al, 1982] and NK cell activity Bukowski et al, 1984;Shellam et al, 1985) control infection within 48 h of infection, before T cell responses reach maximum activity. In contrast, the more susceptible BALB/c mice rely on CD8 ÷ T cellmediated immunity for the control of MCMV infection (Reddehase et at, I985, 1987).…”

Antibody Responses to Murine Cytomegalovirus in Genetically Resistant and Susceptible Strains of Mice

“…Interferon titres were determined by reduction of the c.p.e, caused by encephalomyocarditis virus on L929 cells as described elsewhere (Allan & Shellam, 1985). A mouse interferon standard (G-002-904-511) was included in every assay and had a mean titre of 1.2 x 104 international reference units/ml (NIH, Bethesda, Md., U.S.A.).…”

Cytomegalovirus hepatitis: characterization of the inflammatory infiltrate in resistant and susceptible mice

“…CBA (H-2'') mice survive challenge with 20-fold higher doses of MCMV than are tolerated by BALB/c (H-2'') mice. This is attributed to the intrinsic resistance of H-2'' cells to MCMV infection [32] and effective interferon [33] and NK cell responses [34].…”