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Beta interferon plus gamma interferon efficiently reduces acyclovir-resistant herpes simplex virus infection in mice in a T-cell-independent manner.
- Source :
-
The Journal of general virology [J Gen Virol] 2010 Mar; Vol. 91 (Pt 3), pp. 591-8. Date of Electronic Publication: 2009 Nov 11. - Publication Year :
- 2010
-
Abstract
- Acyclovir (ACV)-resistant herpes simplex virus type 1 (HSV-1) causes severe diseases in immunocompromised patients, so identification of new therapies is needed. Interferons (IFNs) are used to treat several other viral infections in the clinic, and IFN-beta and IFN-gamma are known to cooperatively reduce wild-type HSV-1 replication in the corneas of immunocompetent mice. Because IFN-gamma has been shown to exert an antiviral effect mostly through T cells, whether combined IFN treatment can still inhibit ACV-resistant HSV-1 replication, especially in immunocompromised hosts, is unknown. The present study evaluated the efficacy of combined IFN treatment on ACV-resistant HSV-1 mutants. In vitro results showed that IFN-beta acted synergistically with IFN-gamma to inhibit HSV-1 replication in both human and mouse cell lines. Some ACV-resistant mutants were actually hypersensitive to combined IFN treatment. In vivo results showed that topical treatment with a low dose of IFN-beta plus IFN-gamma (200 U each) on mouse corneas efficiently reduced the viral loads by up to 4, 4 and 3 logs, respectively, in the eyes, trigeminal ganglia and brainstems of wild-type and also immunocompromised nude mice infected or co-infected with ACV-resistant HSV-1 in a manner independent of T cells. A highly efficient reduction in HSV acute replication by combined IFN treatment led to a dramatic decrease in subsequent virus reactivation from neural tissues, trigeminal ganglia, brainstems and spinal cords of latently infected mice. Thus, a combination of IFN-beta and IFN-gamma could be a potential treatment for ACV-resistant HSV-1 in immunocompromised patients.
- Subjects :
- Animals
Antiviral Agents pharmacology
Brain Stem virology
Cell Line
Cornea virology
Drug Therapy, Combination
Herpes Simplex virology
Herpesvirus 1, Human drug effects
Humans
Mice
Mice, Inbred ICR
Mice, Nude
Treatment Outcome
Trigeminal Ganglion virology
Viral Load
Virus Replication drug effects
Acyclovir pharmacology
Antiviral Agents therapeutic use
Drug Resistance, Viral
Herpes Simplex drug therapy
Interferon-beta therapeutic use
Interferon-gamma therapeutic use
T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1465-2099
- Volume :
- 91
- Issue :
- Pt 3
- Database :
- MEDLINE
- Journal :
- The Journal of general virology
- Publication Type :
- Academic Journal
- Accession number :
- 19906941
- Full Text :
- https://doi.org/10.1099/vir.0.016964-0