INTERFERONIHOITO PUUTIAISAIVOKUUMEESEEN

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Lähettäjä: Soijuv Lähetetty: 1.10.2005 18:48

3 puutiaisaivokuumetta koskevaa tutkimusta.


J Virol. 2005 Oct;79(20):12828-39. Related Articles, Links

Inhibition of Interferon-Stimulated JAK-STAT Signaling by a Tick-Borne
Flavivirus and Identification of NS5 as an Interferon Antagonist.

Best SM, Morris KL, Shannon JG, Robertson SJ, Mitzel DN, Park GS, Boer
E, Wolfinbarger JB, Bloom ME.

Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories,
NIAID, NIH, 903 S. Fourth St., Hamilton, MT 59840. s...@niaid.nih.gov.

The tick-borne encephalitis (TBE) complex of viruses, genus Flavivirus,
can cause severe encephalitis, meningitis, and/or hemorrhagic fevers.
Effective interferon (IFN) responses are critical to recovery from
infection with flaviviruses, and the mosquito-borne flaviviruses can
inhibit this response. However, little is known about interactions
between IFN signaling and TBE viruses. Langat virus (LGTV), a member of
the TBE complex of viruses, was found to be highly sensitive to the
antiviral effects of IFN. However, LGTV infection inhibited IFN-induced
expression of a reporter gene driven by either IFN-alpha/beta- or
IFN-gamma-responsive promoters. This indicated that LGTV can inhibit
the IFN-mediated JAK-STAT (Janus kinase-signal transducer and activator
of transcription) pathway of signal transduction. The mechanism of
inhibition was due to blocks in the phosphorylation of both Janus
kinases, Jak1 and Tyk2, during IFN-alpha signaling and at least a
failure of Jak1 phosphorylation following IFN-gamma stimulation. To
determine the viral protein(s) responsible, we individually expressed
all nonstructural (NS) proteins and examined their ability to inhibit
signal transduction. Expression of NS5 alone inhibited STAT1
phosphorylation in response to IFN, thus identifying NS5 as a potential
IFN antagonist. Examination of interactions between NS5 and cellular
proteins revealed that NS5 associated with IFN-alpha/beta and -gamma
receptor complexes. Importantly, inhibition of JAK-STAT signaling and
NS5-IFN receptor interactions were demonstrated in LGTV-infected human
monocyte-derived dendritic cells, important target cells for early
virus replication. Because NS5 may interfere with both innate and
acquired immune responses to virus infection, this protein may have a
significant role in viral pathogenesis.
PMID: 16188985 [PubMed - in process]

1: Vopr Virusol. 2001 Jan-Feb;46(1):25-8. Related Articles, Links

Comparative in vitro study of the effectiveness of various
immunomodulating substances in tick-borne encephalitis

[Article in Russian]

Krylova NV, Leonova GN.

Suppressing effect of tick-borne encephalitis (TBE) virus on expression
of lymphocyte subpopulation receptors has been demonstrated in vitro.
Effects of 14 immunomodulators on expression of T lymphocyte receptors
under the effect of TBE virus have been compared. Anti-TBE
immunoglobulin, 4-iodantipyrin, and leukinferon had the highest
protective effect after a preventive injection. Thymalin and
leukinferon in combination with human leukocytic interferon were the
most effective within the treatment protocols. Further studies of
sensitivity of immunoregulator cells to immunomodulators is recommended
with the aim of adding these drugs to therapy of TBE patients.

PMID: 11233283 [PubMed - indexed for MEDLINE]

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1: Vopr Virusol. 2000 Jan-Feb;45(1):33-7. Related Articles, Links

Protective effect of a new antiviral preparation of phosprenyl in
experimental tick-borne encephalitis

[Article in Russian]

Ozherelkov SV, Timofeev AV, Novikova GP, Deeva AV, Narovlianskii AN,
Sanin AV, Pronin AV.

Antiviral activity of phosprenyl was studied in BALB/c mice infected
with tick-borne encephalitis (TBE) virus. Up to 60% animals infected
with TBE virus survived after 1-3 intramuscular injections of
phosprenyl. The mortality in the untreated group infected with the
virus was 100%. Direct antiviral effect of phosprenyl was studied in
sensitive SPEV cells infected with TBE virus. The titer of the virus
decreased 10-fold in the cells treated with the drug vs. untreated
control cells. Phosprenyl stimulates some interleukins:
gamma-interferon, tumor necrosis factor-alpha, and interleukin-6. The
stimulating effect of the drug manifests in intact animals and in those
infected with TBE virus and treated with phosprenyl. The prospects of
further trials of the drug as a therapeutic and prophylactic agent in
TBE are discussed.

PMID: 10695042 [PubMed - indexed for MEDLINE]