TY - JOUR
T1 - Macrophages from endotoxin-hyporesponsive (Lps(d)) C3H/HeJ mice are permissive for vesicular stomatitis virus because of reduced levels of endogenous interferon
T2 - Possible mechanism for natural resistance to virus infection
AU - Vogel, S. N.
AU - Fertsch, D.
PY - 1987
Y1 - 1987
N2 - The C3H/HeJ mouse strain bears an autosomal gene defect, Lps(d), which results in a greatly diminished capacity to respond to endotoxin, the ubiquitous lipolysaccharide derived from the cell walls of gram-negative bacteria. These mice also exhibit greater susceptibility to a variety of viral and bacterial infections than syngeneic, fully lipopolysaccharide-responsive (Lps(n)) mouse strains and possess macrophages with defects in differentiation which are reversed by treatment with exogenous interferon (IFN). To test directly the hypothesis that C3H/HeJ macrophages are deficient in endogenous IFN levels, macrophages from C3H/HeJ (Lps(d)) and C3H/OuJ (Lps(n)) mice were compared for sensitivity to vesicular stomatitis virus. At a multiplicity of infection of 0.1, C3H/OuJ macrophages were completely refractory to infection, whereas C3H/HeJ macrophages were permissive for replication, and infection resulted in 100% cytopathic effect. These findings were confirmed with a second inbred Lps(n) and Lps(d) strain pair. Levels of 2',5'-oligoadenylate synthetase were significantly higher in Lps(n) cells. C3H/HeJ macrophages, derived from bone marrow precursors under the influence of macrophage colony-stimulating factor, show previously to induce IFN in macrophages, were as refractory as C3H/OuJ macrophages. Exposure of nonpermissive macrophages to anti-IFN-α/β antibody prior to infection rendered cells permissive. Our findings suggest that endotoxin provides a primary stimulus for the maintenance of normal macrophage differentiation and innate resistance via the induction of endogenous IFN by macrophages.
AB - The C3H/HeJ mouse strain bears an autosomal gene defect, Lps(d), which results in a greatly diminished capacity to respond to endotoxin, the ubiquitous lipolysaccharide derived from the cell walls of gram-negative bacteria. These mice also exhibit greater susceptibility to a variety of viral and bacterial infections than syngeneic, fully lipopolysaccharide-responsive (Lps(n)) mouse strains and possess macrophages with defects in differentiation which are reversed by treatment with exogenous interferon (IFN). To test directly the hypothesis that C3H/HeJ macrophages are deficient in endogenous IFN levels, macrophages from C3H/HeJ (Lps(d)) and C3H/OuJ (Lps(n)) mice were compared for sensitivity to vesicular stomatitis virus. At a multiplicity of infection of 0.1, C3H/OuJ macrophages were completely refractory to infection, whereas C3H/HeJ macrophages were permissive for replication, and infection resulted in 100% cytopathic effect. These findings were confirmed with a second inbred Lps(n) and Lps(d) strain pair. Levels of 2',5'-oligoadenylate synthetase were significantly higher in Lps(n) cells. C3H/HeJ macrophages, derived from bone marrow precursors under the influence of macrophage colony-stimulating factor, show previously to induce IFN in macrophages, were as refractory as C3H/OuJ macrophages. Exposure of nonpermissive macrophages to anti-IFN-α/β antibody prior to infection rendered cells permissive. Our findings suggest that endotoxin provides a primary stimulus for the maintenance of normal macrophage differentiation and innate resistance via the induction of endogenous IFN by macrophages.
UR - http://www.scopus.com/inward/record.url?scp=0023140939&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0023140939&partnerID=8YFLogxK
U2 - 10.1128/jvi.61.3.812-818.1987
DO - 10.1128/jvi.61.3.812-818.1987
M3 - Article
C2 - 2433468
AN - SCOPUS:0023140939
SN - 0022-538X
VL - 61
SP - 812
EP - 818
JO - Journal of virology
JF - Journal of virology
IS - 3
ER -