The EBV-HIV interrelationship and the value of EBV-DNA analysis

<p>Epstein-Barr virus (EBV) infects the vast majority of humans and resides latently in B-cells. This virus carries genes that can induce and sustain mature B cell growth. EBV is associated with a wide range of B-cell lymphomas including Burkitt lymphoma and non Hodgkin lymphoma (NHL) in human immunodeficiency virus 1 (HIV-1) infected patients. Latent EBV infection in B lymphocytes is a risk factor for B-cell lymphomas in conditions of combined antigen stimulation and immunosuppression as with Burkitts lymphoma in malaria endemic African regions and non Hodgkin lymphoma in HIV-1 infected patients. In the era of modern combination antiretroviral therapy (cART) there has been an impressive reduction of Acquired Immunodeficiency syndrome (AIDS)-related opportunistic infections and lymphomas, although patients still suffer an increased risk for NHL. This work is based on EBV-DNA load measurement in blood as a tool to analyse EBV-host relationship in HIV-1 infection.</p><p>In general HIV-1 infected individuals have a higher EBV-DNA load and symptomatic HIV-1 infected even higher. Individual variables, immunological factors and treatments as cART affect this pattern. In one of our studies we identified one group and one risk factor that influenced EBV-DNA load. HIV-1 infected individuals with a history of a symptomatic primary infection in combination with induced immune stimulation by therapeutic vaccination/adjuvant showed an increased load. Without the vaccination/adjuvant stimuli this group did not show the same increase. HIV-1 infected patients with a history of a symptomatic primary infection might therefore be at risk for developing NHL. Therapeutic vaccination/adjuvant increases the EBV- DNA load and we regard this immunomodulation as a risk factor. Different pattern of EBV- host restoration by cART was seen in a long term follow of patients with increased EBV-DNA load after vaccination. The EBV-host relation seems to be reconditioned by successful cART treatment, measured by the CD4+ cell count returning to normal levels, with some reservation for the functional restoration, together with remaining undetectable HIV-1 RNA. For individuals with unsuccessful cART treatment the distinct decrease of EBV-DNA could not be seen. In a patient treated for EBV positive plasmablastic lymphoma we observed a sharp increase of EBV-DNA load before clinical signs of recurrence.</p><p>Measurement of EBV-DNA load is valuable in monitoring disease progression in HIV-1 infected patients. After cART treatment the dynamics of EBV-DNA load reveal if the antiviral treatment is suboptimal, even if breakthroughs detected as HIV RNA peaks are missed. When an EBV positive tumour is treated successfully EBV-DNA monitoring can be of importance to observe early signs of relapse. Monitoring EBV-DNA load during therapeutic vaccination studies seems highly motivated. In conclusion EBV-DNA load analysis is a useful additional instrument to monitor different groups of HIV-1 patients with increased risk for lymphoma development.</p><h3>List of scientific papers</h3><p>I. Anna M.C. Friis, Katarina Gyllensten, Anna Aleman, Ingemar Ernberg, and Börje Åkerlund. The Effect of Antiretroviral Combination Treatment on Epstein-Barr Virus (EBV) Genome Load in HIV-Infected Patients. Viruses. 2010; 2: 867–879. <br><a href="https://doi.org/10.3390/v2040867">https://doi.org/10.3390/v2040867</a><br><br> </p><p>II. Anna M.C. Friis, Börje Åkerlund, Katarina Gyllensten, Anna Aleman, Ingemar Ernberg. Host-Epstein-Barr virus relationship affected by immunostimulation in HIV-infected patients representing distinct progressor profile groups. Scand J Infect Dis. 2012 May; 44(5):388-92. <br><a href="https://doi.org/10.3109/00365548.2011.645503">https://doi.org/10.3109/00365548.2011.645503</a><br><br> </p><p>III. Anna M.C. Friis, Börje Åkerlund, Katarina Gyllensten, Anna Aleman, Eric Sandström, Göran Bratt, Ingemar Ernberg. Epstein-Barr virus genome load is increased by therapeutic vaccination in HIV-l carriers, and further enhanced after a history of symptomatic primary infection. [Submitted]</p><p>IV. Anna M.C. Friis, Birger Christensson, Katarina Gyllensten, Anna Aleman, Jie-Zhi Zou, Börje Åkerlund, Ingemar Ernberg. EBV-DNA analysis in blood predicts disease progression in a rare case of plasmablastic lymphoma with effusion. [Manuscript]</p>