Interferon-induced expression of MxA in the respiratory tract of rhesus macaques is suppressed by influenza virus replication.
To determine the relationship between influenza A virus replication and innate antiviral immune responses, rhesus monkeys were given oseltamivir before influenza A/Memphis/7/01 (H1N1) challenge. We found that oseltamivir treatment significantly reduced viral replication in the trachea (p < 0.029). Further, in the trachea of both treated and untreated monkeys the mRNA levels of most innate antiviral molecules in the IFN-alphabeta pathway were dramatically increased by 24 h postinfection. However, the mRNA level of a single IFN-stimulated gene, MxA (myxovirus resistance A), the IFN-stimulated gene known to be critical in blocking influenza virus replication, was significantly lower in the tracheal lavages of untreated monkeys than in the oseltamivir-treated monkeys (p = 0.05). These results demonstrate for the first time that uncontrolled influenza A virus replication actively suppresses MxA gene expression and emphasize the critical role of innate immunity in controlling influenza virus replication in vivo.
Carroll
Timothy D
TD
California National Primate Research Center, and Center for Comparative Medicine, University of California-Davis, One Shields Avenue, Davis, CA 95616, USA.
Matzinger
Shannon R
SR
Genescà
Meritxell
M
Fritts
Linda
L
Colòn
Roxana
R
McChesney
Michael B
MB
Miller
Christopher J
CJ
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D001831:Body Temperature; D002460:Cell Line; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D007372:Interferons / Q000502:physiology*; D008253:Macaca mulatta; D064547:Myxovirus Resistance Proteins; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D012333:RNA, Messenger / Q000096:biosynthesis; D014132:Trachea / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D014779:Virus Replication / Q000276:immunology*
D000914:Antibodies, Viral; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger; D007372:Interferons; D019204:GTP-Binding Proteins