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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.
Medical Microbiology and Immunology ( IF 5.4 ) Pub Date : 2019-10-04 , DOI: 10.1007/s00430-019-00637-2
Juliana Prado Gonçales 1 , Thaísa Regina Rocha Lopes 1 , Virginia Maria Barros de Lorena 2 , Melayne Rocha Aciole 1 , José Valter Joaquim Silva Júnior 3, 4 , Tania Regina Tozetto-Mendoza 5 , Paulo Henrique Braz-Silva 6 , Maria Rosangela Cunha Duarte Coêlho 1, 7
Affiliation  

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.

中文翻译:

艾滋病毒/艾滋病患者中NFκB和相关细胞因子与病毒载量和针对HHV-8的抗体的产生相关。

人类γ疱疹病毒8(HHV-8)复制受到病毒和宿主元素之间复杂相互作用的影响。在这里,我们评估了艾滋病毒/艾滋病患者(PLHA)中B(CD19 +)和T(CD3 +)淋巴细胞中NFκB和TNF-α的表达以及IL-1β和IL-12细胞因子的血清浓度,对HHV-8相关疾病呈阴性,并呈递针对HHV-8的潜伏性或裂解性抗原的抗体。此外,我们还评估了HHV-8病毒载量与NFκB,TNF-α,IL-1β和IL-12水平的相关性。NFκB(p  <0.0001)或TNF-α(p  <0.0001)在B淋巴细胞(CD19 +)和IL-1β(p  <0.0266)和IL-12(p <0.0001)的浓度与针对HHV-8裂解抗原的抗体的存在有关。CD19 +NFκB+TNF-α+和CD3 +NFκB+TNF-α+细胞也与溶胞感染抗体的存在有关(p  <0.0001)。在所有评估的PLHA中,只有溶血抗体效价最高的个体(即1:320)具有可检测的HHV-8病毒载量。其中,HHV-8病毒载量与NFκB(r  = 0.6,p  = 0.003)和TNF-α(r  = 0.5,p  = 0.01)(在CD19 +淋巴细胞中)和IL-1β(r  = 0.5)相关,p  = 0.01)和IL-12(r  = 0.6,p = 0.006)水平。我们认为,病毒复制和/或再激活除了与针对HHV-8的裂解抗体的发展有关外,还可能与通过NFκB引起的炎症反应有关。最后,尽管以前免疫应答失衡与HHV-8相关疾病有关,但我们的结果表明,在HHV-8个体中可以清楚地观察到免疫力的重要变化,主要是炎症反应,但尚未出现临床表现。
更新日期:2019-10-04
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