Archives of Virology

, Volume 163, Issue 4, pp 987–995 | Cite as

Antiviral effect of lithium chloride on replication of avian leukosis virus subgroup J in cell culture

Original Article


Lithium chloride (LiCl) has been reported to possess antiviral activity against several viruses. In the current study, we assessed the antiviral activity effect of LiCl on ALV-J infection in CEF cells by using real-time PCR, Western blot analysis, IFA and p27 ELISA analysis. Our results showed that both viral RNA copy number and protein level decreased significantly in a dose and time dependent manner. Time-course analysis revealed that the antiviral effect was more pronounced when CEFs were treated at the post infection stage rather than at early absorption or pre-absorption stages. Further experiments demonstrated that LiCl did not affect virus attachment or entry, but rather affected early virus replication. We also found that inhibition of viral replication after LiCl treatment was associated with reduced mRNA levels of pro-inflammatory cytokines. These results demonstrate that LiCl effectively blocked ALV-J replication in CEF cells and may be used as an antiviral agent against ALV-J.



The research was supported by the National Key Research and Development Program of China (Grant No. 2017YFD0500702), the Key Program of NSFC-Henan Joint Fund (U1604232), NCFC-RCUK-BBSRC (Grant No. 31761133002), the National Natural Science Foundation of China (Grant No. 31772734), the Newton Fund Project on “UK-China Centre of Excellence for Research on Avian Diseases”, Chinese Special Fund for Agro scientific Research in the Public Interest (201203055), the PAPD of the Jiangsu Higher Education Institutions and the Jiangsu Co-innovation Centre for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses.

Authors’ contributions

Kun Qian and Aijian Qin designed the study. Kun Qian, Xiaowei Cheng and Danyang Zhang carried out the experiments, analyzed the data, and drafted the manuscript. Aijian Qin supervised all the experiments and participated in the data analysis. Hongxia Shao, Yongxiu Yao and Venugopal Nair discussed and prepared the final report. All of the authors have read and approved the final manuscript.

Compliance with ethical standards

Conflict of interests

The authors declare no conflict of interest.

Ethical approval

The experimental protocols for preparing primary chicken embryo fibroblasts were approved by the Animal Care and Protection Committee of Yangzhou University (reference number SYXX2012-0020).


  1. 1.
    Ballanger F, Tenaud I, Volteau C, Khammari A, Dreno B (2008) Anti-inflammatory effects of lithium gluconate on keratinocytes: a possible explanation for efficiency in seborrhoeic dermatitis. Arch Dermatol Res 300(5):215–223CrossRefPubMedGoogle Scholar
  2. 2.
    Baril M, Es-Saad S, Chatel-Chaix L, Fink K, Pham T, Raymond VA, Audette K, Guenier AS, Duchaine J, Servant M, Bilodeau M, Cohen E, Grandvaux N, Lamarre D (2013) Genome-wide RNAi screen reveals a new role of a WNT/CTNNB1 signaling pathway as negative regulator of virus-induced innate immune responses. PLoS Pathog 9(6):e1003416CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Chen K, Wu Y, Zhu M, Deng Q, Nie X, Li M, Wu M, Huang X (2013) Lithium chloride promotes host resistance against Pseudomonas aeruginosa keratitis. Mol Vis 19:1502–1514PubMedPubMedCentralGoogle Scholar
  4. 4.
    Chen Y, Kong D, Cai G, Jiang Z, Jiao Y, Shi Y, Li H, Wang C (2016) Novel antiviral effect of lithium chloride on mammalian orthoreoviruses in vitro. Microb Pathog 93:152–157CrossRefPubMedGoogle Scholar
  5. 5.
    Chen Y, Yan H, Zheng H, Shi Y, Sun L, Wang C, Sun J (2015) Antiviral effect of lithium chloride on infection of cells by porcine parvovirus. Adv Virol 160(4):1015–1020Google Scholar
  6. 6.
    Cui J, Xie J, Gao M, Zhou H, Chen Y, Cui T, Bai X, Wang H, Zhang G (2015) Inhibitory effects of lithium chloride on replication of type II porcine reproductive and respiratory syndrome virus in vitro. Antiviral Ther 20(6):565–572CrossRefGoogle Scholar
  7. 7.
    Cui Z, Sun S, Zhang Z, Meng S (2009) Simultaneous endemic infections with subgroup J avian leukosis virus and reticuloendotheliosis virus in commercial and local breeds of chickens. Avian Pathol 38(6):443–448CrossRefPubMedGoogle Scholar
  8. 8.
    De Meyer I, Martinet W, Van Hove CE, Schrijvers DM, Hoymans VY, Van Vaeck L, Fransen P, Bult H, De Meyer GR (2011) Inhibition of inositol monophosphatase by lithium chloride induces selective macrophage apoptosis in atherosclerotic plaques. Br J Pharmacol 162(6):1410–1423CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Ding Y, Dou J, Teng Z, Yu J, Wang T, Lu N, Wang H, Zhou C (2014) Antiviral activity of baicalin against influenza A (H1N1/H3N2) virus in cell culture and in mice and its inhibition of neuraminidase. Adv Virol 159(12):3269–3278Google Scholar
  10. 10.
    Everall IP, Bell C, Mallory M, Langford D, Adame A, Rockestein E, Masliah E (2002) Lithium ameliorates HIV-gp120-mediated neurotoxicity. Mol Cell Neurosci 21(3):493–501CrossRefPubMedGoogle Scholar
  11. 11.
    Hao HP, Wen LB, Li JR, Wang Y, Ni B, Wang R, Wang X, Sun MX, Fan HJ, Mao X (2015) LiCl inhibits PRRSV infection by enhancing Wnt/beta-catenin pathway and suppressing inflammatory responses. Antiviral Res 117:99–109CrossRefPubMedGoogle Scholar
  12. 12.
    Harrison SM, Tarpey I, Rothwell L, Kaiser P, Hiscox JA (2007) Lithium chloride inhibits the coronavirus infectious bronchitis virus in cell culture. Avian Pathol 36(2):109–114CrossRefPubMedGoogle Scholar
  13. 13.
    Hu X, Ye J, Qin A, Zou H, Shao H, Qian K (2015) Both MicroRNA-155 and virus-encoded MiR-155 ortholog regulate TLR3 expression. PLoS One 10(5):e0126012CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Kumar A, Zloza A, Moon RT, Watts J, Tenorio AR, Al-Harthi L (2008) Active beta-catenin signaling is an inhibitory pathway for human immunodeficiency virus replication in peripheral blood mononuclear cells. J Virol 82(6):2813–2820CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Letendre SL, Woods SP, Ellis RJ, Atkinson JH, Masliah E, van den Brande G, Durelle J, Grant I, Everall I (2006) Lithium improves HIV-associated neurocognitive impairment. AIDS (London, England) 20(14):1885–1888CrossRefGoogle Scholar
  16. 16.
    Li X, Lin W, Chang S, Zhao P, Zhang X, Liu Y, Chen W, Li B, Shu D, Zhang H, Chen F, Xie Q (2016) Isolation, identification and evolution analysis of a novel subgroup of avian leukosis virus isolated from a local Chinese yellow broiler in South China. Adv Virol 161(10):2717–2725Google Scholar
  17. 17.
    Li X, Liu Y, Wu T, Jin Y, Cheng J, Wan C, Qian W, Xing F, Shi W (2015) The antiviral effect of baicalin on enterovirus 71 in vitro. Viruses 7(8):4756–4771CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Li YP, Bang DD, Handberg KJ, Jorgensen PH, Zhang MF (2005) Evaluation of the suitability of six host genes as internal control in real-time RT-PCR assays in chicken embryo cell cultures infected with infectious bursal disease virus. Vet Microbiol 110(3–4):155–165CrossRefPubMedGoogle Scholar
  19. 19.
    Machado-Vieira R, Manji HK, Zarate CA Jr (2009) The role of lithium in the treatment of bipolar disorder: convergent evidence for neurotrophic effects as a unifying hypothesis. Bipolar Disord 11(Suppl 2):92–109CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Mei M, Ye J, Qin A, Wang L, Hu X, Qian K, Shao H (2015) Identification of novel viral receptors with cell line expressing viral receptor-binding protein. Sci Rep 5:7935CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Nunes PV, Forlenza OV, Gattaz WF (2007) Lithium and risk for Alzheimer’s disease in elderly patients with bipolar disorder. Br J Psychiatry 190:359–360CrossRefPubMedGoogle Scholar
  22. 22.
    Oruch R, Elderbi MA, Khattab HA, Pryme IF, Lund A (2014) Lithium: a review of pharmacology, clinical uses, and toxicity. Eur J Pharmacol 740:464–473CrossRefPubMedGoogle Scholar
  23. 23.
    Payne LN, Nair V (2012) The long view: 40 years of avian leukosis research. Avian Pathol 41(1):11–19CrossRefPubMedGoogle Scholar
  24. 24.
    Pietruczuk K, Jozwik A, Ruckemann-Dziurdzinska K, Bryl E, Witkowski JM (2009) Cytoprotective effect of lithium against spontaneous and induced apoptosis of lymphoid cell line MOLT-4. Folia Histochem Cytobiol 47(4):639–646PubMedGoogle Scholar
  25. 25.
    Qian K, Gao AJ, Zhu MY, Shao HX, Jin WJ, Ye JQ, Qin AJ (2014) Genistein inhibits the replication of avian leucosis virus subgroup J in DF-1 cells. Virus Res 192:114–120CrossRefPubMedGoogle Scholar
  26. 26.
    Ren X, Meng F, Yin J, Li G, Li X, Wang C, Herrler G (2011) Action mechanisms of lithium chloride on cell infection by transmissible gastroenteritis coronavirus. PLoS One 6(5):e18669CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Rychlik I, Karasova D, Sebkova A, Volf J, Sisak F, Havlickova H, Kummer V, Imre A, Szmolka A, Nagy B (2009) Virulence potential of five major pathogenicity islands (SPI-1 to SPI-5) of Salmonella enterica serovar Enteritidis for chickens. BMC Microbiol 9:268CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Singh N, Halliday AC, Thomas JM, Kuznetsova OV, Baldwin R, Woon EC, Aley PK, Antoniadou I, Sharp T, Vasudevan SR, Churchill GC (2013) A safe lithium mimetic for bipolar disorder. Nat Commun 4:1332CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Skinner GR, Hartley C, Buchan A, Harper L, Gallimore P (1980) The effect of lithium chloride on the replication of herpes simplex virus. Med Microbiol Immunol 168(2):139–148CrossRefPubMedGoogle Scholar
  30. 30.
    Wang F, Wang X, Chen H, Liu J, Cheng Z (2011) The critical time of avian leukosis virus subgroup J-mediated immunosuppression during early stage infection in specific pathogen-free chickens. J Vet Sci 12(3):235–241CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Wang X, Zhao P, Cui ZZ (2012) Identification of a new subgroup of avian leukosis virus isolated from Chinese indigenous chicken breeds. Chin J Virol 28(6):609–614Google Scholar
  32. 32.
    Wu X, Qian K, Qin A, Shen H, Wang P, Jin W, Eltahir YM (2010) Recombinant avian leukosis viruses of subgroup J isolated from field infected commercial layer chickens with hemangioma and myeloid leukosis possess an insertion in the E element. Vet Res Commun 34(7):619–632CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Zhao FR, Xie YL, Liu ZZ, Shao JJ, Li SF, Zhang YG, Chang HY (2017) Lithium Chloride inhibits early stages of foot-and-mouth disease virus (FMDV) replication in vitro. J Med VirolGoogle Scholar
  34. 34.
    Zhou P, Fu X, Yan Z, Fang B, Huang S, Fu C, Hong M, Li S (2015) Antiviral effect of lithium chloride on infection of cells by canine parvovirus. Adv Virol 160(11):2799–2805Google Scholar
  35. 35.
    Ziaie Z, Kefalides NA (1989) Lithium chloride restores host protein synthesis in herpes simplex virus-infected endothelial cells. Biochem Biophys Res Commun 160(3):1073–1078CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  • Kun Qian
    • 1
    • 2
    • 3
    • 5
  • Xiaowei Cheng
    • 1
  • Danyang Zhang
    • 1
  • Hongxia Shao
    • 1
    • 2
    • 3
  • Yongxiu Yao
    • 4
    • 5
  • Venugopal Nair
    • 4
    • 5
  • Aijian Qin
    • 1
    • 2
    • 3
    • 5
  1. 1.Ministry of Education Key Lab for Avian Preventive Medicine, College of Veterinary MedicineYangzhou UniversityYangzhouPeople’s Republic of China
  2. 2.Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and ZoonosesYangzhouPeople’s Republic of China
  3. 3.Jiangsu Key Lab of ZoonosisYangzhouPeople’s Republic of China
  4. 4.Avian Oncogenic virus groupThe Pirbright InstitutePirbrightUK
  5. 5.The UK-China Centre of Excellence for Research on Avian DiseasesBinzhouPeople’s Republic of China

Personalised recommendations