Abstract

BackgroundMost HIV-infected persons are cytomegalovirus (CMV) seropositive and retain latent virus that can be reactivated by immune activation. Their T cell populations express markers reflecting a late stage of differentiation, but the contributions of HIV and CMV to this profile are unclear. We investigated the immunological “footprint” of CMV in HIV patients who had a history of extreme immunodeficiency but were now stable on antiretroviral therapy (ART).ResultsTwenty CMV seropositive HIV patients >50 years old with nadir CD4 T-cell counts <200 cells/μl were studied after >12 years on ART. 16 CMV seropositive and 9 CMV seronegative healthy controls were included. CMV antibody titres were higher in HIV patients than controls (P < 0.001-0.003). Levels of soluble B-cell activating factor (sBAFF) were elevated in patients (P = 0.002) and correlated with levels of CMV antibodies (P = 0.03-0.002), with no clear relationship in controls. CD8 T-cell IFNγ responses to the IE1 peptide (VLE) remained elevated in HIV patients (P = 0.005). The CD57+CD45RA+CD27− phenotype of CD8 T-cells correlated with age (r = 0.60, P = 0.006), antibodies against CMV IE1 protein (r = 0.44, P = 0.06) and CD4 T-cell IFNγ response to CMV lysate (r = 0.45, P = 0.05).ConclusionsHumoral and T-cell responses to CMV remained elevated in HIV patients after >12 years on ART. Age and presence of CMV disease influenced CD8 T-cell phenotypes. Elevated levels of sBAFF may be a consequence of HIV disease and contribute to high titres of CMV antibody.Electronic supplementary materialThe online version of this article (doi:10.1186/s12979-015-0041-0) contains supplementary material, which is available to authorized users.

Highlights

  • Most human immunodeficiency virus -1 (HIV)-infected persons are cytomegalovirus (CMV) seropositive and retain latent virus that can be reactivated by immune activation

  • CMV lysate, CMV glycoprotein B (gB) and CMV Immediate Early-1 (IE1) antibody titres are higher in HIV patients than healthy controls and more tightly correlated The study focuses on the long term outcome for CMV seropositive HIV patients stable on antiretroviral therapy (ART)

  • Levels of antibodies reactive with CMV lysate, CMV gB and CMV IE1 were higher in HIV patients than CMV+ controls (Table 1)

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Summary

Introduction

Most HIV-infected persons are cytomegalovirus (CMV) seropositive and retain latent virus that can be reactivated by immune activation. Their T cell populations express markers reflecting a late stage of differentiation, but the contributions of HIV and CMV to this profile are unclear. Immune activation may promote the reactivation of CMV leading to the re-stimulation of CMVspecific T-cells [1] This creates T-cell populations enriched with differentiated, apoptosis-resistant memory T cells with limited proliferative capabilities, and leaves an immune system with limited capacity to recognize novel antigens [2]. Persistent viral infections, inflammatory syndromes and ageing induce the accumulation of Affandi et al Immunity & Ageing (2015) 12:14 highly differentiated memory T cells re-expressing CD45RA [13].

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