CORRELATION BETWEEN CD4 LYMPHOCYTES, VIRAL LOAD AND L-LYSINE PLASMA LEVEL IN HIV-INFECTED PATIENTS

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Abstract

Introduction.HIV-infection is associated with significant pathological changes of the host metabolic processes, such as energy dysfunction, dyslipidemia, protein catabolic effects and amino acid imbalance, which ultimately form the polymorphism of clinical symptoms of the disease. The significant disturbances of protein and lipid metabolism are widely described in asymptomatic and advanced stage HIV-infected patients, but infection-related amino acid abnormalities is not fully explored. The further research of HIV impact on the host metabolic processes in particular, the plasma amino acid profile, are essential for understanding the pathophysiology of HIV-infection. Our aim was to determine the association between CD4 lymphocytes, viral load and plasma L-lysine levels in clinical stages HIV-infected patients. Material and methods.A total of 750 HIV-1-infected males before highly active antiretroviral therapy (HAART) monitored in our center. The patients were classified into four stages of the disease 3, 4a, 4b and 4c, according to the classification system for HIV-infection in Russian Federation (2006). Quantitative HIV-1 RNA assay was performed using (RT-PCR) reverse-transcriptase polymerase chain reaction. The plasma L-lysine levels were assessed by thin layer chromatography (TLC). Results. We observed that plasma L-lysine concentrations markedly decreased with the clinical stages of HIV-infection. Low levels of essential amino acid were found in 57% of HIV-infected subjects in the asymptomatic stage (3), 67% and 68% in the advanced stages (4a and 4b, 4c, respectively). Our data revealed that plasma amino acid concentrations were positively correlated with CD4 count lymphocytes (P < 0.01) and inversely with HIV viral load (P < 0.05) in the total cohort. The mean L-lysine acid levels were significantly lower in advanced stage (4a and 4b, 4c) HIV-infected patients than in controls and asymptomatic stage (3) patients (P < 0.01 and P < 0.001, respectively). Conclusion. There was evidence of the association between plasma L-lysine and HIV-1 RNA level, immunological markers and clinical stages of HIV-infection among the entire cohort. The results show that advanced stages of HIV-infection are characterized by significant changes in plasma L-lysine concentrations with the disease stages of HIV-infection. Levels of this basic amino acid negatively correlating with viral load and inversely with CD4 count lymphocytes. These findings are important for understanding the pathophysiology of HIV-infection and the development of new approaches in the treatment. Although the mechanism is at present conjectural, the influence of plasma L-lysine on the HIV-1 RNA levels must be considered and remains to be proved. 

About the authors

E. V. Butorov

The Municipal Center of HIV/AIDS prophylaxis, Surgut, Russian Federation

Author for correspondence.
Email: butorov888@gmail.com

PhD (Medicine), Clinical Epidemiologist, Clinical Pathologist, The Municipal Center of HIV/AIDS Prophylaxis, Surgut, Russian Federation 

Russian Federation

References

  1. Бышевский А.Ш., Галян С.Л., Терсенев О.А. Биохимические сдвиги и их оценка в диагностике патологических состояний. М.: Медицинская книга, 2002. 318 с. [Byshevskiy A.Sh., Galyan S.L., Tersenev O.A. Biokhimicheskie sdvigi i ikh otsenka v diagnostike patologicheskikh sostoyanii [Biochemical changes and their evaluation in the diagnosis of pathological states]. Moscow: Medical book, 2002, 318 p.]
  2. Alireza A., Tahereh S. Hyperhomocysteinemia in HIV-infected individuals: correlation of a frequent prothrombotic factor with CD4+ cell count. Oman. Med. J., 2012, vol. 27, no. 3, pp. 224–227. doi: 10.5001/omj.2012.50
  3. Beisel W.R., Sawyer W.D., Ryll E.D., Crozier D. Metabolic effects of intracellular infections in man. Ann. Internal Med., 1967, vol. 67, pp. 744–779. doi: 10.7326/0003-4819-67-4-744
  4. Everitt E., Sundquist B., Philipson L. Mechanism of the arginine requirement for adenovirus synthesis // I. Synthesis of structural protein. J. Virol., 1971, vol. 8, pp. 742–753.
  5. Fafournoux P., Bruhat A., Jousse C. Amino acid regulation of gene expression. Biochem. J., 2000, vol. 351, no. 1, pp. 1–12.
  6. Fuchs D., Möller A.A., Reibnegger G., Stöckle E., Werner E.R., Wachter H. Decreased serum tryptophan in patients with HIV-1 infection correlates with increased serum neopterin and with neurologic/psychiatric symptoms. J. Acquir. Immune Defic. Syndr., 1990, vol. 3, no. 9, pp. 873–876.
  7. Grunfeld C., Feingold K. Metabolic disturbances and wasting in the acquired immunodeficiency syndrome. N. Engl. J. Med., 1992, vol. 327, no. 5, pp. 329–37. doi: 10.1056/neim199207303270506
  8. Guo F., Cen S., Niu M., Javanbakht H., Kleiman L. Specific inhibition of the synthesis of human Lysyl-tRNA synthetase results in decreases in tRNALys incorporation, tRNALys annealing to viral RNA, and viral infectivity in human immunodeficiency virus type 1. J. Virol., 2003, vol. 77, no. 18, pp. 9817–9822.
  9. Hortin G.L., Landt M., Powderly W.G. Changes in plasma amino acid concentrations in response to HIV-1 infection. Clin. Chem., 1994, vol. 40, no. 5, pp. 785–789.
  10. Ikeda K., Yamasaki H., Suzuki Y., Hajime K.A., Arakawa T. Novel strategy with acidic arginine solution for the treatment of influenza a virus infection (Review). Exp. Ther. Med., 2010, vol. 1, no. 2, pp. 251–256. doi: 10.3892/etm_00000039
  11. Inglis V.B.M. Requirement of arginine for the replication of herpes virus. J. Gen. Virol., 1968, vol. 3, pp. 9–17. doi: 10.1099/0022-1317-3-1-9
  12. The GAP Report. Joint United Nations Programme on HIV/AIDS (UNAIDS), 2014, 422 p.
  13. Kilberg M.S., Hutson R.G., Laine R.O. Amino acid-regulated gene expression in eukaryotic cells. FASEB J., 1994, vol. 8, no. 1, pp. 13–19.
  14. Kotler D.P., Tierney A.R., Wang J., Pierson R.N. Magnitude of body-cell-mass depletion and the timing of death from wasting in AIDS. Am. J. Clin. Nutr., 1989, vol. 50, pp. 444–447.
  15. Laurichesse H., Tauveron I., Gourdon F., Cormerais L., Champredon C., Charrier S., Rochon C., Lamain S., Bayle G., Laveran H., Thieblot P., Beytout J., Grizard J. Threonine and methionine are limiting amino acids for protein synthesis in patients with AIDS.J. Nutr., 1998, vol. 128, no. 8, pp. 1342–1348.
  16. Loh P.C., Oie H.K. Role of lysine in the replication of reovirus: I. Synthesis of complete and empty virions. J. Virol., 1969, vol. 4, no. 6, pp. 890–895.
  17. Lukasheva E.V., Berezov T.T. L-Lysine alpha-oxidase: physico-chemical and biological properties. Biochemistry, 2002, vol. 67, no. 10, pp. 1394–1402.
  18. Maeda J., Higashiyama M., Imaizumi A., Nakayama T., Yamamoto H., Daimon T., Yamakado M., Imamura F., Kodama K. Possibility of multivariate function composed of plasma amino acid profiles as a novel screening index for non-small cell lung cancer: a case control study. BMC Cancer, 2010, vol. 10, p. 690. doi: 10.1186/1471-2407-10-690
  19. Naito T., Irie H., Tsujimoto K., Ikeda K., Arakawa T., Koyama A.H. Antiviral effect of arginine against herpes simplex virus type 1. Int. J. Mol. Med., 2009, vol. 23, no. 4, pp. 495–499. doi: 10.3892/ijmm_00000156
  20. Pisters P.W., Brennan M.F. Amino acid metabolism in human cancer cachexia. Review. Annu. Rev. Nutr., 1990, vol. 10, pp. 107–132. doi: 10.1146/annurev.nu.10.070190.000543
  21. Schneider R.J., Shenk T. Impact of virus infection on host cell protein synthesis. Annu. Rev. Biochem., 1987, vol. 56, pp. 317–332. doi: 10.1146/annurev.bi.56.070187.001533
  22. Sherman I.W. Amino acid metabolism and protein synthesis in malarial parasites. Bull. World Health Organ., 1977, vol. 55, no. 2–3, pp. 265–276.
  23. Tankersley R.W. Amino acid requirements of herpes simplex virus in human cells. J. Bacteriol., 1964, vol. 87, pp. 609–613.
  24. Tisne C., Roques B.P., Dardel F. The annealing mechanism of HIV-1 reverse transcription primer onto the viral genome. J. Biol. Chem., 2004, vol. 279, no. 5, pp. 3588–3595.
  25. Wannemacher R.W.Jr. Key role of various individual amino acids in host response to infection. Am. J. Clin. Nutr., 1977, vol. 30, no. 8, pp. 1269–1280.
  26. Wannemacher R.W.Jr., Pekarek J.R., Bartelloni P.J., Vollmer R.T., Beisel W.R. Changes in individual plasma amino acids following experimentally induced sand fly fever virus infection. Metabolism, 1972, vol. 21, no. 1, pp. 67–76. doi: 10.1016/0026-0495(72)90021-2
  27. Wheeler D.A., Gibert C.L., Launer C.A., Muurahainen N., Elion R.A., Abrams D.I., Bartsch G.E. Weight loss as a predictor of survival and disease progression in HIV infection. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol., 1998, vol. 18, pp. 80–85.
  28. Wigand R., Kümel G. Amino acid requirement of adenovirus multiplication. J. Gen. Virol., 1978, vol. 39, pp. 281–292. doi: 10.1099/0022-1317-39-2-281
  29. Yamasaki H., Tsujimoto K., Koyama A.H., Ejima D., Arakawa T. Arginine facilitates inactivation of enveloped viruses. J. Pharm. Sci., 2008, vol. 97, no. 8, pp. 3067–3073. doi: 10.1002/jps.21224

Copyright (c) 2015 Butorov E.V.

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