Assessment of the relationship between Epstein–Barr virus major types and genovariants as well as clinical and laboratory parameters in HIV-infected adults

Abstract

Introduction. People living with human immunodeficiency virus (HIV) are more likely to experience Epstein-Barr virus (EBV) reactivation and develop EBV-associated diseases. In Russia, the clinical significance of EBV genetic diversity in HIV-infected patients has not been assessed. The aim was to analyze a relationship between the major EBV types and LMP-1 genovariants with clinical and laboratory parameters in HIV-infected subjects. Materials and methods. Peripheral blood leukocytes were collected from 138 HIV(+) individuals aged 20-69 years. Association between EBV types, LMP-1 variants and subvariants with clinical and laboratory parameters (CD4+ T-lymphocyte count, HIV and EBV viral load, use and adherence to antiretroviral therapy (ART)), was performed using the principal component analysis method and the Mann-Whitney U test. Results. It has been shown that detectable HIV viral load increases in patients with low CD4+ T-lymphocyte counts, high EBV viral load, and low or no ART adherence. In general, infection with EBV-2 or the LMP-1 B95-8 alone resulted in lower EBV and HIV viral loads compared with other variants. Significant EBV-1 LMP-1 subvariants were identified, the biological potential of which was enabled in immunodeficiency state (CD4+ T-lymphocyte count ≤200 cells/μl). In “naive” patients, EBV-1/LMP-1(S309N)+HIV co-infection occurred with a higher, and EBV-1/LMP-1(E328Q)+HIV with the lowest HIV viral load. The highest EBV DNA concentrations were observed with EBV-1/LMP-1(Q334R)+HIV. In “experienced” patients, the level of EBV DNA was significantly lower when infected with EBV-1/LMP-1(E328Q)+HIV and, conversely, higher in case of detected EBV-1/LMP-1(H358P)+HIV. Conclusion. The features of clinical and laboratory parameters EBV+HIV co-infection caused by different EBV-1 LMP-1 subvariants (at the level of amino acid substitutions S309N, E328Q, Q334R, H358P) have been identified. It is necessary to study the functional role of such mutations in vitro and in vivo. In the context of assessing a clinical significance of EBV molecular genetic diversity, it is advisable to conduct larger-scale studies in different territories of Russia.