Premium
STAT1 and STAT3 α/β splice form activation predicts host responses in mouse hepatitis virus type 3 infection
Author(s) -
Ning Qin,
Berger Lloyd,
Luo Xiaoping,
Yan Weiming,
Gong Feili,
Dennis James,
Levy Gary
Publication year - 2003
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.10290
Subject(s) - stat1 , stat protein , stat3 , virology , biology , virus , spleen , immune system , microbiology and biotechnology , interferon , gene , immunology , biochemistry
Signal transducer and activator of transcription 1α (STAT1 α) is reported to be essential for IFN‐γ and IFN‐α regulated gene expression, while STAT1 β, an alternate splice‐form, mediates only IFN‐α‐dependent gene expression. STAT3 α and STAT3 β splice forms are also differentially activated in response to cytokines including IL‐6 and IL‐10. The aim of this study was to investigate whether the STAT activation will predict the host immune response to viral infection and possibly a therapeutic target for the treatment of viral infection. Mouse hepatitis virus type 3 (MHV‐3) resistant strain (A/J) and sensitive mouse strains (BalB/cJ) were infected intraperitoneally (i.p.) with 100 plaque form units (pfu) of MHV‐3. The mice were sacrificed at the indicated times, and livers and spleens were immediately frozen in liquid nitrogen. Nuclear extracts proteins were detected by immunoblotting. STAT1 and STAT3 activation in spleen increased 24 to 72 hr following MHV‐3 infections in both sensitive and resistant mouse strains. However, over this time period, the ratio of activated α to β splice‐form for STAT1 and STAT3 increased above 1.0 in resistant A/J mice, while the ratio fell to <0.3 in MHV‐3 sensitive Balb/cJ and C3H/HeJ strains. Activated STAT1 α/β and STAT3 α/β ratio in liver were similar in resistant and sensitive mouse strains. Treatment of sensitive Balb/cJ mice with neutralizing anti‐TGF‐β antibody could increase the STAT1 α/β ratio to <1.0 in spleens, predicting enhanced rates of survival. These results suggested that ratio of activated STAT1 α/β and STAT3 α/β in mixed leukocytes from spleen predict the outcome to MHV‐3 infection, and may be an important marker and therapeutic target for modification of host immune response to virus infection. J. Med. Virol. 69:306–312, 2003. © 2003 Wiley‐Liss, Inc.