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Association of NFκB and related-cytokines with the viral load and development of antibodies against HHV-8 in people living with HIV/AIDS

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Abstract

Human gammaherpesvirus 8 (HHV-8) replication is influenced by a complex interaction between viral and host elements. Here, we evaluated the expression of NFκB and TNF-α in B (CD19 +) and T (CD3 +) lymphocytes, and the serum concentration of IL-1β and IL-12 cytokines in people living with HIV/AIDS (PLHA), negative for HHV-8-related diseases, and who presented antibodies to latent or lytic antigens from HHV-8. In addition, we also evaluated the correlation of HHV-8 viral load with NFκB, TNF-α, IL-1β and IL-12 levels. The expression of NFκB (p < 0.0001) or TNF-α (p < 0.0001) in B lymphocytes (CD19 +) and the IL-1β (p < 0.0266) and IL-12 (p < 0.0001) concentrations were associated with the presence of antibodies to HHV-8 lytic antigens. The CD19 + NFκB + TNF-α + and CD3 + NFκB + TNF-α + cells were also associated with the presence of antibodies to lytic infection (p < 0.0001). Among all PLHA evaluated, only individuals with the highest titers of lytic antibodies, i.e., 1:320, had detectable HHV-8 viral load. In these, HHV-8 viral load was correlated to NFκB (r = 0.6, p = 0.003) and TNF-α (r = 0.5, p = 0.01) (both in CD19 + lymphocytes) and with IL-1β (r = 0.5, p = 0.01) and IL-12 (r = 0.6, p = 0.006) levels. We believe that viral replication and/or reactivation, in addition to being associated with the development of lytic antibodies against HHV-8, may be associated with inflammatory response via NFκB. Finally, although immune response imbalance has been previously related to HHV-8-associated diseases, our results indicate that important changes in immunity, mainly in the inflammatory response, may be clearly observed in individuals with HHV-8, but who have not yet presented clinical manifestations.

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Acknowledgements

Lopes TRR and Gonçales JP are supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) fellowships. Silva Júnior J.V.J. is supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). The authors thank all patients who accepted to participate of the study and the Program for Technological Development in Tools for HealthPDTIS-FIOCRUZ for use of its facilities.

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Authors and Affiliations

  1. Virology Sector, Laboratory of Immunopathology Keizo Asami, Federal University of Pernambuco, Av. Prof. Moraes Rego, s/n. Cidade Universitária, Recife, PE, CEP: 50670-901, Brazil

    Juliana Prado Gonçales, Thaísa Regina Rocha Lopes, Melayne Rocha Aciole & Maria Rosangela Cunha Duarte Coêlho

  2. Department of Immunology, Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Recife, Pernambuco, Brazil

    Virginia Maria Barros de Lorena

  3. Virology Sector, Department of Preventive Veterinary Medicine, Federal University of Santa Maria, Santa Maria, Rio Grande do Sul, Brazil

    José Valter Joaquim Silva Júnior

  4. Department of Microbiology and Parasitology, Federal University of Santa Maria, Santa Maria, Rio Grande do Sul, Brazil

    José Valter Joaquim Silva Júnior

  5. Laboratory of Virology, Institute of Tropical Medicine of São Paulo, University of São Paulo, São Paulo, Brazil

    Tania Regina Tozetto-Mendoza

  6. Division of Pathology, Department of Stomatology, School of Dentistry, University of São Paulo, São Paulo, Brazil

    Paulo Henrique Braz-Silva

  7. Department of Physiology and Pharmacology, Center of Biosciences, Federal University of Pernambuco, Recife, Pernambuco, Brazil

    Maria Rosangela Cunha Duarte Coêlho

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  1. Juliana Prado Gonçales
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Correspondence to Maria Rosangela Cunha Duarte Coêlho.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee. The study was approved by the Research Ethics Committee of the Health Sciences Center at the Federal University of Pernambuco (Protocol Number: 45156215.5.0000.5208). Informed consent was obtained from all participants included in the study.

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Gonçales, J.P., Lopes, T.R.R., de Lorena, V.M.B. et al. Association of NFκB and related-cytokines with the viral load and development of antibodies against HHV-8 in people living with HIV/AIDS. Med Microbiol Immunol 209, 41–49 (2020). https://doi.org/10.1007/s00430-019-00637-2

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