Role of IFN-alpha/beta signaling in the prevention of genital herpes virus type 2 infection.

• This study has shown that IFN-alpha/beta signaling is crucial for combating primary herpes simplex virus type 2 (HSV-2) infection and for responding to immunotherapy using ligands to TLR3, 7 and 9, but not for vaccine-induced immunity. Both genital viral replication and the disease progression were enhanced in HSV-2-infected mice lacking the IFN-alpha/beta receptor (IFN-alpha/betaR-/-). IFN-alpha/betaR-/- mice were, however, able to mount a normal HSV-2-specific Th1 response and acquired sterilizing immunity following vaccination. Anti-viral treatments using agonists to TLR3, 7 and 9 by administration of synthetic dsRNA, imiquimod and oligonucleotides containing unmethylated CpG motifs, respectively, were strongly dependent on IFN-alpha/beta receptor signaling for their efficacy. Even though all treatments had a weak impact on local vaginal viral replication in infected IFN-alpha/betaR-/- animals, they did not affect disease progression or mortality in these animals as opposed to wild type controls where all three treatments reduced viral replication as well as disease severity and mortality. Lack of IFN-alpha/betaR signaling also blocked production of IFN-gamma and TNF-alpha in response to TLR9 activation. These studies have shown that IFN-alpha/beta receptor signaling is important for multiple events in the anti-viral defense.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

Nyckelord

Animals

Antiviral Agents

therapeutic use

Female

Herpes Genitalis

drug therapy

immunology

metabolism

virology

Herpesvirus 2

Human

immunology

metabolism

Interferon Type II

immunology

metabolism

Interferon-alpha

immunology

metabolism

therapeutic use

Interferon-beta

immunology

metabolism

therapeutic use

Mice

Poly I-C

pharmacology

Receptor

Interferon alpha-beta

metabolism

Signal Transduction

Toll-Like Receptors

agonists

metabolism

physiology

therapeutic use

Tumor Necrosis Factor-alpha

metabolism

interferon; toll-like receptors; herpes simplex virus type 2; cytokines; protection

MEDICINE

Publikations- och innehållstyp

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art (ämneskategori)