The importance of the JAK/STAT signaling pathway in
antiviral immunity has been addressed extensively in
mammals [1], and increasing evidence has suggested that
this pathway also plays a role in invertebrate organisms
during virus infection [2–4]. Activation of the JAK/STATyrosine residue near the carboxyl terminus. The tyrosinephosphorylated
STATs then dimerize and translocate to the
nucleus, where they transcriptionally activate appropriate
genes to mediate various responses, including cell growth,
cell differentiation and immune responses [5].
The immune responses mediated by the JAK/STAT pathway
have been widely studied in model organisms. Genetic knockout
studies of mice suggested that the mammalian JAK/STAT
signaling pathway is predominant in controlling immune
responses, especially the antiviral response [6]. In insects,
the first evidence of the JAK/STAT pathway being involved in
immune responses was in the mosquito Anopheles gambiae,
whereas in mammals, AgSTAT translocated into the nucleus of
the fat body cell upon bacterial infection [7]. When Drosophila
is challenged by bacteria, the JAK/STAT pathway activates at
least two gene families, TEP and TOT, that are involved in
innate immunity [8,9]. The transcriptional profile of Drosophila
C Virus-infected Drosophila further suggests that the JAK/STAT
pathway might also respond to viral infection [10]. Taken
together, these data suggest that in addition to the Toll and
Imd pathways, the JAK/STAT pathway could be a third
evolutionarily conserved pathway that supports innate
immunity in insects. Because the JAK/STAT pathway plays a
significant antiviral role, it follows that this pathway might be
targeted by a virus that is attempting to evade the host’s
immune responses; and in fact, several viruses have been
shown to counter their hosts’ antiviral mechanisms by
inhibiting the JAK/STAT signaling pathway. For example, the
V protein of simian virus targets its host’s STAT1 for
degradation [11], while the human cytomegalovirus targets
JAK1 for degradation [12]. Infection with the varicella-zoster
virus inhibits the expression of both STAT1 and JAK2 [13].
Hepatitis C virus also inhibits host immunity by disrupting the
crosstalk between the MAPK and JAK/STAT pathways [14].
WSSV also targets STAT, but instead of inhibiting or
disrupting its activity, WSSV exploits the host STAT by using
it to bind to the promoter region of the WSSV immediate
early gene ie1 and thus enhance ie1 transcription [2]. To
better understand how the JAK/STAT pathway generally
responds to pathogens in shrimp, in the present study, we
first cloned and characterized the full-length cDNA sequence
of shrimp STAT from Penaeus monodon. Next, real-time RTPCR
was used to investigate whether the transcription level
of STAT was changed after Litopenaeus vannamei were
challenged with WSSV and the immune stimulants LPS and
PGN (lipopolysacharide and peptidoglycan). A previous study
had used EMSA to show that WSSV infection led to increased
levels of activated STAT, so when our RT-PCR results showed
that STAT transcription was reduced after challenge with
WSSV, we used two other more direct methods (a phosphorylation
status analysis and an immunostaining assay) to
reconfirm the activation status of STAT in lymphoid organ
cells of WSSV-infected shrimp.
The importance of the JAK/STAT signaling pathway inantiviral immunity has been addressed extensively inmammals [1], and increasing evidence has suggested thatthis pathway also plays a role in invertebrate organismsduring virus infection [2–4]. Activation of the JAK/STATyrosine residue near the carboxyl terminus. The tyrosinephosphorylatedSTATs then dimerize and translocate to thenucleus, where they transcriptionally activate appropriategenes to mediate various responses, including cell growth,cell differentiation and immune responses [5].The immune responses mediated by the JAK/STAT pathwayhave been widely studied in model organisms. Genetic knockoutstudies of mice suggested that the mammalian JAK/STATsignaling pathway is predominant in controlling immuneresponses, especially the antiviral response [6]. In insects,the first evidence of the JAK/STAT pathway being involved inimmune responses was in the mosquito Anopheles gambiae,whereas in mammals, AgSTAT translocated into the nucleus ofthe fat body cell upon bacterial infection [7]. When Drosophilais challenged by bacteria, the JAK/STAT pathway activates atleast two gene families, TEP and TOT, that are involved ininnate immunity [8,9]. The transcriptional profile of DrosophilaC Virus-infected Drosophila further suggests that the JAK/STATpathway might also respond to viral infection [10]. Takentogether, these data suggest that in addition to the Toll andImd pathways, the JAK/STAT pathway could be a thirdevolutionarily conserved pathway that supports innateimmunity in insects. Because the JAK/STAT pathway plays asignificant antiviral role, it follows that this pathway might betargeted by a virus that is attempting to evade the host’simmune responses; and in fact, several viruses have beenshown to counter their hosts’ antiviral mechanisms byinhibiting the JAK/STAT signaling pathway. For example, theV protein of simian virus targets its host’s STAT1 fordegradation [11], while the human cytomegalovirus targetsJAK1 for degradation [12]. Infection with the varicella-zostervirus inhibits the expression of both STAT1 and JAK2 [13].Hepatitis C virus also inhibits host immunity by disrupting thecrosstalk between the MAPK and JAK/STAT pathways [14].WSSV also targets STAT, but instead of inhibiting ordisrupting its activity, WSSV exploits the host STAT by usingit to bind to the promoter region of the WSSV immediateearly gene ie1 and thus enhance ie1 transcription [2]. Tobetter understand how the JAK/STAT pathway generallyresponds to pathogens in shrimp, in the present study, wefirst cloned and characterized the full-length cDNA sequenceof shrimp STAT from Penaeus monodon. Next, real-time RTPCRwas used to investigate whether the transcription levelof STAT was changed after Litopenaeus vannamei werechallenged with WSSV and the immune stimulants LPS andPGN (lipopolysacharide and peptidoglycan). A previous studyhad used EMSA to show that WSSV infection led to increasedlevels of activated STAT, so when our RT-PCR results showedthat STAT transcription was reduced after challenge withWSSV, we used two other more direct methods (a phosphorylationstatus analysis and an immunostaining assay) toreconfirm the activation status of STAT in lymphoid organcells of WSSV-infected shrimp.
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