Down-regulation of Bgp1(a) viral receptor by interferon-gamma is related to the antiviral state and resistance to mouse hepatitis virus 3 infection.
Together with the evidence that the reduced virus growth and the antiviral state induced by interferon (IFN)-gamma, occurring only in macrophages from resistant animals, correlated with the decrease of MHV3 binding to macrophage membrane proteins, we show here the expression of cellular and viral genes in resistant (A/J) and susceptible (BALB/c) mouse macrophages after IFN-gamma activation/infection. The expression of interferon response gene 47 and interferon regulatory factor 1 genes takes place after IFN-gamma activation in both macrophages, indicating their activation. The expression of the biliary glycoprotein 1(a) (Bgp1(a), the main virus receptor) decreased only in IFN-gamma-activated A/J mouse macrophages, in contrast to the expression of the Bgp2 (alternative receptor), which was not influenced by IFN-gamma activation. The synthesis of both viral mRNA and virus particles was delayed only in IFN-gamma-activated A/J mouse macrophages compared with susceptible BALB/c macrophages. Besides the evidence that IFN-gamma may modulate the expression of the Bgp1(a) isoform of carcinoembryonic antigen family, these data show that IFN-gamma, which induces resistance against MHV3 infection, may be involved in the down-regulation of the main viral receptor expression, a key step forward in our understanding of the molecular basis of resistance against virus infection.
Vassão
R C
RC
Instituto Butantan, São Paulo, 05503-900, Brazil.
de Franco
M T
MT
Hartz
D
D
Modolell
M
M
Sippel
A E
AE
Pereira
C A
CA
D000818:Animals; D015703:Antigens, CD; D000998:Antiviral Agents / Q000276:immunology* / Q000378:metabolism; D015815:Cell Adhesion Molecules; D002478:Cells, Cultured; D015536:Down-Regulation; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism; D007700:Kinetics; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D006517:Murine hepatitis virus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
D015703:Antigens, CD; D000998:Antiviral Agents; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D012333:RNA, Messenger; D012367:RNA, Viral; D011991:Receptors, Virus; D007371:Interferon-gamma