Effect of Interleukin-28B polymorphism on Interleukin-28 expression and immunological recovery amongst HIV-1-infected individuals following antiretroviral therapy

Indian J Med Microbiol. 2017 Oct-Dec;35(4):580-584. doi: 10.4103/ijmm.IJMM_17_299.

Abstract

Purpose: Type III interferon is well known to have diverse antiviral and immunomodulatory activities. Studies describing the association of interleukin (IL)-28 polymorphisms in treatment-experienced HIV participants are limited. This study was aimed to determine the association of IL-28B gene polymorphisms with immunological recovery in HIV patients on 6-9 months of antiretroviral therapy (ART).

Methods: Eighty treatment-naive HIV patients were recruited, of which 48 patients were followed up after 6-9 months of ART. Whole blood samples were collected before and after 6-9 months of ART. CD4, CD8 and CD3 counts were enumerated flow cytometry. IL-28B polymorphisms (rs12979860 and rs8099917) were profiled by polymerase chain reaction (PCR)-restriction fragment length polymorphism. The IL-28 mRNA and plasma HIV-1 viral load were estimated using real-time PCR and plasma IL-28 level by ELISA.

Results: The CD4, CD4/CD3%, IL-28 mRNA and reversal of CD4/CD8 ratio were significantly increased following 6-9 months of ART (P < 0.01). The rs12979860 CC genotype and rs12979860:rs8099917 (CC: TT) haplotype showed significant association with higher CD4+ T-cell count amongst treatment-naive HIV-infected individuals (P < 0.05). In addition, there was a significant association of rs12979860 CC genotype with increase in CD4/CD3% following 6-9 months of ART. IL-28 mRNA showed correlation with the HIV-1 viral load, and there was a significant increase in the IL-28 mRNA expression following 6-9 months of ART.

Conclusion: Our preliminary findings suggest that IL-28 polymorphisms could influence both immunological recovery and therapeutic response in HIV infection. Hence, functional studies are warranted to understand the mechanistic basis of IL-28-mediated host genetic influence on HIV therapeutic response.

MeSH terms

  • Adult
  • Aged
  • Anti-Retroviral Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active*
  • CD4-CD8 Ratio
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Follow-Up Studies
  • Genotype
  • HIV Infections / drug therapy*
  • HIV Infections / genetics
  • HIV Infections / immunology*
  • Humans
  • Interferons
  • Interleukins / biosynthesis*
  • Interleukins / genetics*
  • Longitudinal Studies
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Polymorphism, Restriction Fragment Length
  • T-Lymphocyte Subsets / immunology
  • Treatment Outcome
  • Young Adult

Substances

  • Anti-Retroviral Agents
  • interferon-lambda, human
  • Interleukins
  • Interferons