Efficacy of low-dose oral use of type I interferon in cytomegalovirus infections in vivo.
Oral administration of type I interferons (IFNs; murine IFN-alpha and IFN-beta) reduces early replication of murine cytomegalovirus (MCMV) in both the spleen and liver of MCMV-infected BALB/c mice. Examination of a range of doses of IFN (1 to 1000 IU) showed that 10 IU administered daily for 1 week prior to virus infection was optimal for inhibition of MCMV replication. Furthermore, low-dose orally administered IFN (10 IU/day) was effective in mice challenged with lethal and sublethal virus inocula. The antiviral efficacy of low-dose orally administered IFN was not restricted by either the route of virus inoculation or the mouse genotype. Analysis by immunohistochemistry of IFN-alpha receptor-bearing cells of the gastrointestinal tract revealed predominant staining of perivascular smooth muscle and the lamina propria of the anterior tongue, small intestine and rectum. These tissues, dense in IFN-alpha receptor-bearing cells, are likely to be the sites of interaction of the orally administered IFNs with the mucosal immune system. In conclusion, we propose that low-dose oral use of type I IFN therapy may have broad applications in the treatment of CMV infections.
Bosio
E
E
Department of Microbiology, University of Western Australia, Nedlands, Perth.
Beilharz
M W
MW
Watson
M W
MW
Lawson
C M
CM
D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D003586:Cytomegalovirus Infections / Q000188:drug therapy*; D004064:Digestive System / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D007150:Immunohistochemistry; D007370:Interferon Type I / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D017471:Receptors, Interferon / Q000378:metabolism; D016896:Treatment Outcome
D000998:Antiviral Agents; D007370:Interferon Type I; D017471:Receptors, Interferon