СHANGES IN THE CELLULAR IMMUNITY AND THE EXPRESSION OF CCR5, CXCR4 IN HIV-INFECTED PATIENTS IN THE FORMATION OF IMMUNOSUPPRESSION DEPENDING ON THE VIRAL TROPISM

The aim of the study was to establish the features of the cellular immunity and the expression of CCR5 and CXCR4 by T-lymphocytes of blood during the AIDS development in HIV-infected patients depending on the viral tropism. The examined patients were divided in two groups: the 1st group – 34 patients infected by R5 tropic HIV; the 2nd group – 19 patients infected by non R5 tropic HIV. The control group consisted of 16 health persons (3 men, 13 females, the average was 32.5 ± 15.1 years). AIDS was established in patients with the 4th stage of HIV infection (WHO, 2012) and/or at the level of CD4+ T-lymphocytes less than 200 cells/mkl. The immunophenotype of cells was detected by the flow cytofluorometry. Monoclonal antibodies “Becton Dickenson” (USA) were used. HIV tropism was detected by “Amplisens HIV-Resist-Seq” reagents (Russia), FPR = 20 %. The obtained results show that the switching of HIV tropism was associated with immunosuppression enhancement due to a significant decrease of B-lymphocytes in patients without AIDS and T-lymphocytes in patients with AIDS. Patients infected by R5 HIV without antiretroviral therapy had a significantly higher level of cytotoxic Т-lymphocytes in comparison with those infected by non R5 HIV. The development of AIDS in patients with R5 HIV infection was associated with a significant decrease in Т-lymphocytes, T-helpers, activated T-helpers and with an increase in the expression of HLA-DR by T-helpers. The development of AIDS in patients with non R5 HIV infection was associated with a decrease in the CXCR4 expression by blood lymphocytes, CCR5 expression by T-helpers, enhanced T-cell immunity activation due to a higher expression of HLA-DR by blood lymphocytes and Т-lymphocytes, a higher intensity of HLA-DR expression by T-helpers, an increase in the HLA-DR expression by CD8+ lymphocytes, a decrease in the CD4+CD25+ content.

HIV infection, tropism, CCR5, CXCR4, T-lymphocytes, immunosuppression, AIDS, immunity activation

1. Pirozhkov I. A., Smolianinov A. B., Chechetkin A. V., Ivolgin D. A. Polymorphism of the CCR5 gene and resistance to HIV infection. Molecular-genetic examination of the public cord blood register. Vestnik gematologii [The Bulletin of Hematology], 2015, vol. 11, no. 2, pp. 23–24. (in Rusian).

2. Bleul C. C., Wu L., Hoxie J. A., Springer T. A., Mackay C. R. The HIV coreceptors CXCR4 and CCR5 are differentially expressed and regulated on human T lymphocytes. Proceedings of the National Academy of Sciences of the United States of America, 1997, vol. 94, pp. 1925–1930.

3. Taborda Natalia A., Hernández Juan C., Lajoie Julie, Juno Jennifer A., Kimani Joshua, Rugeles María T., Fowke Keith R. Low expression of activation and inhibitory molecules on NK cells and CD4+ T cells is associated with viral control. AIDS Research and Human Retroviruses, 2015, vol. 31 (6), pp. 636–640. doi:10.1089/aid.2014.0325.

4. Li-Chung Tsao, Haitao Guo, Jerry Jeffrey, James A. Hoxie and Lishan Su CCR5 interaction with HIV-1 env contributes to env-induced depletion of CD4 T cells in vitro and in vivo. Retrovirology, 2016, vol. 13, pp. 22. doi 10.1186/s12977-016-0255-z.

5. Fenyö E. M., Esbjörnsson J., Medstrand P., Jansson M. J. Human immunodeficiency virus type 1 biological variation and coreceptor use: from concept to clinical significance. Internal Medicine Journal, 2011, vol. 270 (6), pp. 520–531. doi: 10.1111/j.1365-2796.2011.02455.x. Epub 2011 Oct. 27.

6. Matievskaia N. V., Tokunova I. O., Kireev D. E. N. V. Detection tropism on and subtypes of HIV on nucleotide sequence of V3 loop protein gp120 env gene of HIV-1. Zdravookhranenie [Healthcare], 2017, no. 1, pp. 4–9. (in Rusian).

7. Matievskaia N. V. Co-infection HIV/HCV: etiology, еpidemiology, рathogenesis, clinic, diagnostics, treatment. Grodno, Grodnenskii gosudarstvennyi meditsinskii universitet [Grodno State Medical University], 2013, 352 p. (in Rusian).

8. Matievskaia N. V., Kireev D. Y., Dmitrjukova M. Ju., Tikunova I. O., Kondratovich I. A. Clinical, immunological, and epidemiological features of HIV infection depending on the tropism of HIV-1. HIV Infection and Immunosuppressive Disorders, 2015, vol. 7, no. 1, рр. 52–59. (in Rusian).

9. Chevalier M. F., Weiss L. The split personality of regulatory T cells in HIV infection. Blood, 2013, vol. 121, no. 1, pp. 29–37.

10. Chachage M., Pollakis G., Kuffour E. O., Haase K., Bauer A., Nadai Y., Podola L., Clowes P., Schiemann M., Henkel L., Hoffmann D., Joseph S., Bhuju S., Maboko L., Sarfo F. S., Eberhardt K., Hoelscher M. CD25+ FoxP3+ memory CD4 T cells are frequent targets of HIV Infection in vivo. Journal of Virology, 2016, vol. 90, no. 20, pp. 8954–8967. doi:10.1128/JVI.00612-16.

11. Lin Y. L., Portales P., Segondy M., Baillat V., de Boever C. M., Le Moing V., Réant B., Montes B., Clot J., Reynes J., Corbeau P. CXCR4 overexpression during the course of HIV-1 infection correlates with the emergence of X4 strains. Journal of Acquired Immune Deficiency Syndromes, 2005, vol. 39, no. 5, pp. 530–536.

12. Fiser A. L., Vincent T., Brieu N., Lin Y. L., Portalès P., Mettling C., Reynes J., Corbeau P., Fiser A. L., Vincent T., Brieu N., Portalès P., Mettling C., Reynes J., Corbeau P. High CD4(+) T-cell surface CXCR4 density as a risk factor for R5 to X4 switch in the course of HIV-1 infection. Journal of Acquired Immune Deficiency Syndromes, 2010, vol. 55, no. 5, pp. 529–535. doi:10.1097/QAI.0b013e3181f25bab.