Higher Type 1 Interferon Levels in Plasma of Asymptomatic HIV-2 than in HIV-1 Individuals

Abstract

A number of cytokines are secreted during HIV infection that enhances both innate and adaptive immune responses. Interferon-α/β/γ, IL-12, IL-15 and IL-18 have been found to contribute to the development, maturation, differentiation and function of NK and other immune cells. The levels of IFN-α/β/γ, IL-12, IL-15 and IL-18 were compared in the plasma of 90 HIV-1 infected and 90 HIV-2 infected subjects by ELISA or Cytometric Beads Array assays. The HIV-infected subjects were stratified according to CD4 + T cell counts into three groups: >500, 200 -500 and <200 cells/ul, with 30 subjects in each group. Cytokine levels were also determined in the plasma of 50 HIV uninfected blood bank donors. Among the cytokines tested, IFN-α was found to be significantly increased in HIV-2 infected compared to HIV-1 infected subjects at high CD4 + T cell counts (p = 0.001). The levels of IFN-β were seen to differ between the two infections in patients from the category of medium CD4 + T cell counts: this was significantly increased in HIV-2 infected patients (p < 0.001) as well as compared to uninfected controls (p = 0.001). The levels of IFN-γ were similar at all the CD4 + T cell categories except for an increase in HIV-2 infected patients at low CD4 + T cell counts (p = 0.02). The levels of these cytokines were similar in all HIV-1 subjects. Also, the level of IL-12p70 was similar between the two infections but significantly higher in HIV-2 at low compared to medium CD4 + T cells categories (p = 0.047). Similar to IFN-γ and IL-12p70, the levels of both IL-18 and IL-15 were found to be significantly higher in HIV-2 infected patients compared to HIV-1 at low CD4 + T cell counts (p < 0.05). These data show that there is variability in the levels of innate cytokines at different stages of HIV infection but the finding of increased IFN-α in HIV-2 infected S. V. Nuvor et al. 16asymptomatic subjects is consistent with the high innate NK responses previously noted at this stage of infection.

Interferon alpha (IFN-ɑ) among Human Immunodeficiency Virus (HIV) patients exposed to Plasmodium falciparum infection in selected Hospitals in Niger State, Nigeria

“…Another reason for increased levels of IFN-α could be low CD4 count which may be due to the fact that infection of HIV as well as P.falciparumhas been known to induce depletion of CD4 T-cells and to reduce CD8 T-cells causing downmodulation, reduction in T-cell sub-population and defective cell mediated immunity against any microbial infection (Kirinyet, 2019). This study however, contradicts the findings of Nuvor et al (2016) which suggests that high levels of IFN-α may be supporting the persistently high CD4+ T cell numbers in HIV infection from an early stage of infection.…”

“…Interferons (IFNs) are a multigene family of inducible cytokines produced by the host immune system which are among the key molecules in the early defense against infections and are in many cases the first line of resistance to many viral and protozoan infections (McNab et al, 2015;Silva-Barrios and Stager, 2017). IFN-Is, particularly IFN-α, appear to be protective in human infections of P. falciparum (Subramaniam et al, 2015) and HIV infections (Nuvor et al, 2016). Studies have also shown associations between high levels of IFN-α produced early during an infection with protection (Subramaniam et al, 2015).On the other hand, excess production of IFN-α have been shown to cause immunopathology leading to immunosuppression (Davidson et al, 2014;Lukhele et al, 2019).…”