Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • AGI5198 Previous study showed that CXCR plays

    2020-02-06

    Previous study showed that CXCR plays an important role in viral infection and that CXCR1, as an important molecule in CXCR, also plays important roles in viral pathogenesis [[39], [40], [41], [42]]. In mammals, CXCR1 plays an important role in resisting viral infection [43,44], and CXCR1 plays an important role in acute inflammation and innate immunity and is a prototype receptor for inflammatory (induced) cytokines [45]. In rock bream, Oplegnathus fasciatus, the magnitude of the CXCR1 transcripts in head kidney and spleen was increased after in vivo injection with rock bream irido virus, showing the inhibitory effects of CXCR1 on viral replication [46]. In addition, mandarin fish CXCR1 was also shown to inhibit viral replication [47]. A previous study conducted by our group showed that CXCR plays an important antiviral role when SGIV infection occurs in vivo [24]. In this study, CXCR1a overexpression significantly inhibited SGIV replication. The results indicate that CXCR1a may be one of the antiviral factors acting against viral infection. Research in humans has shown that TNF-α can induce the down-regulation of human CXCR1 [48]. In chickens, CXCR1 plays a role in activating the IFN α/β system by binding to various transcription factors in the host response during viral infection [49,50]. In this study, we also found that overexpression of CXCR1a in grouper AGI5198 significantly increased the expression of IFNr and IFNh. In mammals, IL8/CXCR1 signaling is implicated in autoimmunity and human immunodeficiency virus-1 (HIV-1) infection [51,52]. Targeting the IL8/CXCR1 axis therefore represents an attractive therapeutic approach for various diseases. In our study, we found that overexpression of CXCR1a in grouper cells also increased the expression of IL8, This suggest that CXCR1a play an antiviral role in grouper may also through IL8/CXCR1 axis. In mandarin fish, the antiviral function of CXCR1 is mostly due to interactions with interferon and interferon-inducible genes, such as IRF and NF-κB transcription factors [41]. Here, overexpression of CXCR1a in grouper cells significantly increased the expression of interferon regulation factors, including IRF1, IRF3, IRF7, IRF9, and interferon-induced/stimulated genes, including viperin, MXI and MXII. Moreover, the ectopic expression of CXCR1a significantly increased the promoter activity of ISRE and IFN induced by SGIV infection. We speculated that the CXCR1a-induced interferon immune response might contribute greatly to its inhibitory effect on SGIV replication. In summary, full-length cDNA cloning, analyses of the cellular localization, expression, and function of CXCR1a in response to grouper viral infection were performed. Our results indicated that CXCR1a encodes a cytoplasmic protein. Furthermore, ectopic expression significantly inhibited SGIV replication in vitro, and this inhibition was due to its enhancing effect on the host interferon immune response. Our results will contribute greatly to understanding the roles of fish CXCR in viral infection.
    Acknowledgements This work is supported by The Youth Fund Project of National Natural Science Foundation of China (No. 41806151, 41706144, 41806161), China Postdoctoral Science Foundation Grant (2018T110876,2017M622710). We would like to thanks the support of young science and technology talents training fund of South China Agricultural University.
    Introduction The bicyclams are a novel class of highly potent antiviral compounds which selectively inhibit the replication of HIV-1 and HIV-2 (De Clercq et al., 1992, De Clercq et al., 1994). Time-of-addition experiments have indicated that the bicyclams block an early step in the viral replication cycle (De Clercq et al., 1992, De Clercq et al., 1994). Binding studies confined the inhibitory effect on an event following binding, but preceding reverse transcription. AMD3100, previously called JM3100 (De Clercq et al., 1994) or SID791 (De Vreese et al., 1996a, De Vreese et al., 1996b), blocks syncytium formation at a concentration 10–100-fold higher than the concentration required to inhibit virus infection (De Clercq et al., 1992). The envelope gp120 glycoprotein has been considered as the major target molecule for this class of compounds because a number of mutations accumulate in the gp120, especially in the V3–V4 region of viruses that were rendered resistant to the bicyclams (De Vreese et al., 1996a, De Vreese et al., 1996b). The V3 loop is important in the viral fusion process and because recently the gp120 of M-tropic viruses has been demonstrated to interact with CCR-5 (Trkola et al., 1996, Wu et al., 1996), experiments were performed to verify whether AMD3100 did not interact with CCR-5 or with fusin (Berson et al., 1996, Feng et al., 1996), recently named CXCR-4 (Mackay, 1996), the coreceptor for T-tropic HIV-1 and HIV-2 strains.