Inhibitory Effects of Lithium Chloride on Replication of Type II Porcine Reproductive and Respiratory Syndrome Virus in vitro

Background Porcine reproductive and respiratory syndrome (PRRS) is one of the most serious diseases affecting the swine industry worldwide; however, there are no efficient control strategies against PRRS virus (PRRSV) at present. Therefore, development of new antiviral treatment strategies is urgently needed. As reported, lithium chloride (LiCl) can efficiently impair the replication of a variety of viruses, including infectious bronchitis coronavirus (IBV) and transmissible gastroenteritis coronavirus (TGEV). In this report, we explored whether LiCl had the potential to inhibit PRRSV infection. Methods MARC-145 cells were treated with LiCl at various stages of PRRSV life cycle. Virus titration assay was performed to determine the virus infectivity. The expression of viral mRNA and protein was measured by real-time PCR and indirect immunofluorescence assay, respectively. The transcript levels of cytokines were evaluated by real-time PCR. Results LiCl significantly suppressed the synthesis of viral RNA and protein; however, it did not block PRRSV binding and entry. Further studies confirmed that LiCl inhibited PRRSV replication at an early stage and TNF-α, an antiviral cytokine, was significantly increased after LiCl treatment. Thus, we suggested that LiCl inhibited PRRSV infection by up-regulating the level of antiviral cytokine TNF-α at an early infection stage. Conclusions Our findings imply that the LiCl has the potential to be used as anti-PRRSV therapy.

[1]  N. Go Modelling the immune response to the Porcine Respiratory and Reproductive Syndrome virus , 2014 .

[2]  Shuo Su,et al.  Mutagenesis analysis of porcine reproductive and respiratory syndrome virus nonstructural protein 7 , 2013, Virus Genes.

[3]  F. Osorio,et al.  Amino acid residues in the non-structural protein 1 of porcine reproductive and respiratory syndrome virus involved in down-regulation of TNF-α expression in vitro and attenuation in vivo. , 2012, Virology.

[4]  K. Tian,et al.  Emergence and pathogenicity of highly pathogenic Porcine reproductive and respiratory syndrome virus in Vientiane, Lao People’s Democratic Republic , 2012, Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc.

[5]  S. Xiao,et al.  Antiviral activity of type I and type III interferons against porcine reproductive and respiratory syndrome virus (PRRSV). , 2011, Antiviral research.

[6]  F. Meng,et al.  Action Mechanisms of Lithium Chloride on Cell Infection by Transmissible Gastroenteritis Coronavirus , 2011, PloS one.

[7]  J. Lunney,et al.  Porcine reproductive and respiratory syndrome virus: An update on an emerging and re-emerging viral disease of swine , 2010, Virus Research.

[8]  D. Hart,et al.  Porcine proximal tubular cells (LLC‐PK1) are able to tolerate high levels of lithium chloride in vitro: assessment of the influence of 1–20 mM LiCl on cell death and alterations in cell biology and biochemistry , 2010, Cell biology international.

[9]  X. Ren,et al.  Antiviral effect of diammonium glycyrrhizinate and lithium chloride on cell infection by pseudorabies herpesvirus , 2009, Antiviral Research.

[10]  F. Osorio,et al.  The Minor Envelope Glycoproteins GP2a and GP4 of Porcine Reproductive and Respiratory Syndrome Virus Interact with the Receptor CD163 , 2009, Journal of Virology.

[11]  T. Kimman,et al.  Challenges for porcine reproductive and respiratory syndrome virus (PRRSV) vaccinology. , 2009, Vaccine.

[12]  G. Gao,et al.  Porcine Respiratory and Reproductive Syndrome Virus Variants, Vietnam and China, 2007 , 2008, Emerging infectious diseases.

[13]  B. Alman,et al.  Beta-Catenin Signaling Plays a Disparate Role in Different Phases of Fracture Repair: Implications for Therapy to Improve Bone Healing , 2007, PLoS medicine.

[14]  Di Liu,et al.  Emergence of Fatal PRRSV Variants: Unparalleled Outbreaks of Atypical PRRS in China and Molecular Dissection of the Unique Hallmark , 2007, PloS one.

[15]  J. Calvert,et al.  CD163 Expression Confers Susceptibility to Porcine Reproductive and Respiratory Syndrome Viruses , 2007, Journal of Virology.

[16]  Sally M. Harrison,et al.  Lithium chloride inhibits the coronavirus infectious bronchitis virus in cell culture , 2007, Avian pathology : journal of the W.V.P.A.

[17]  R. Mitchell,et al.  Recombinant swine beta interferon protects swine alveolar macrophages and MARC-145 cells from infection with Porcine reproductive and respiratory syndrome virus. , 2007, The Journal of general virology.

[18]  R. Forsberg Divergence time of porcine reproductive and respiratory syndrome virus subtypes. , 2005, Molecular biology and evolution.

[19]  J. Bono,et al.  Interferon type I response in porcine reproductive and respiratory syndrome virus-infected MARC-145 cells , 2004, Archives of Virology.

[20]  J. Domínguez,et al.  Porcine reproductive and respiratory syndrome (PRRS) virus down-modulates TNF-alpha production in infected macrophages. , 2000, Virus research.

[21]  C. Gagnon,et al.  Current knowledge on the structural proteins of porcine reproductive and respiratory syndrome (PRRS) virus: comparison of the North American and European isolates , 2000, Archives of Virology.

[22]  M. Raamsman,et al.  Identification of a Novel Structural Protein of Arteriviruses , 1999, Journal of Virology.

[23]  P. van Oostveldt,et al.  Entry of porcine reproductive and respiratory syndrome virus into porcine alveolar macrophages via receptor-mediated endocytosis. , 1999, The Journal of general virology.

[24]  M. Murtaugh,et al.  Porcine Reproductive and Respiratory Syndrome Virus Comparison: Divergent Evolution on Two Continents , 1999, Journal of Virology.

[25]  E. Snijder,et al.  The molecular biology of arteriviruses. , 1998, The Journal of general virology.

[26]  J. Ávila,et al.  Lithium inhibits Alzheimer's disease‐like tau protein phosphorylation in neurons , 1997, FEBS letters.

[27]  D. Cavanagh Nidovirales: a new order comprising Coronaviridae and Arteriviridae. , 1997, Archives of virology.

[28]  H. Manji,et al.  Signal transduction pathways. Molecular targets for lithium's actions. , 1995, Archives of general psychiatry.

[29]  E. D. de Kluyver,et al.  Characterization of proteins encoded by ORFs 2 to 7 of Lelystad virus , 1995, Virology.

[30]  K. Conzelmann,et al.  Molecular Characterization of Porcine Reproductive and Respiratory Syndrome Virus, a Member of the Arterivirus Group , 1993, Virology.

[31]  F. Wagenaar,et al.  Lelystad virus, the cause of porcine epidemic abortion and respiratory syndrome: a review of mystery swine disease research at Lelystad. , 1992, Veterinary microbiology.

[32]  I. Brown,et al.  'Blue ear' disease of pigs , 1991, Veterinary Record.

[33]  N. A. Kefalides,et al.  Lithium chloride restores host protein synthesis in herpes simplex virus-infected endothelial cells. , 1989, Biochemical and biophysical research communications.