Nazim Fizza, Kayani Hammad Afzal, Ali Nathwani Apsara, Mir Fatima, Abidi Syed Hani
Department of Biological and Biomedical Sciences, Aga Khan University, Karachi 74800, Pakistan.
Department of Biosciences, Shaheed Zulfikar Ali Bhutto Institute of Science and Technology, Karachi 75600, Pakistan.
Viruses. 2022 Aug 19;14(8):1823. doi: 10.3390/v14081823.
(1) Background: CMV and EBV co-infections can affect the HIV disease progression by modulating the immune system. The disease dynamics can differ in HIV-positive adults and children. In Pakistan, HIV is rapidly expanding, especially in children; however, the prevalence of CMV and EBV co-infection and the effect on immune modulation in HIV-positive children are not known. This study aimed to bridge this gap by estimating the rate of active CMV and EBV co-infection in HIV-positive children, followed by the analysis of differential expression of cytokines in HIV mono- and HIV/CMV/EBV co-infected children. (2) Methods: DNA samples from 319 HIV-positive children, previously recruited as part of a study to investigate the HIV outbreak in Larkana, Pakistan, in 2019, were screened for CMV and EBV through qPCR. Subsequently, differences in HIV viral loads and CD4 counts were analyzed between the HIV mono- and HIV/CMV/EBV co-infected groups. The RNA samples were used to determine the differential expression of both pro- and anti-inflammatory cytokines in the mono- and co-infected groups using RT-qPCR, while unpaired T-test and Pearson correlation test were applied to, respectively, analyze the differential cytokine expression and correlation between cytokine in the two groups. (3) Results: Of 319 samples, the rate of active EBV and CMV co-infection in HIV-positive children was observed in 79.9% and 38.9%, respectively. A significant difference was observed in HIV viral load between HIV mono- and co-infected groups. IFN-γ expression was found to be lower in the HIV mono-infected group, while higher in all other three co-infected groups. Meanwhile, mRNA expression of TGF-β1 was found to be lower in HIV mono- and HIV-CMV-EBV co-infected groups, while higher in HIV-CMV and HIV-EBV co-infected groups. IFN-γ and IL-2 exhibited a significant positive correlation in all except HIV-CMV co-infected group. (4) Conclusions: The study suggests that the presence of EBV/CMV co-infection can affect the HIV viral loads and expression of certain cytokines (IFN-γ and TGF-β1), which may affect the HIV disease dynamics in infected children.
(1) 背景：巨细胞病毒（CMV）和EB病毒（EBV）合并感染可通过调节免疫系统影响HIV疾病进展。HIV阳性成人和儿童的疾病动态可能有所不同。在巴基斯坦，HIV感染正在迅速蔓延，尤其是在儿童中；然而，CMV和EBV合并感染的患病率以及对HIV阳性儿童免疫调节的影响尚不清楚。本研究旨在通过估计HIV阳性儿童中活动性CMV和EBV合并感染率来填补这一空白，随后分析HIV单一感染儿童与HIV/CMV/EBV合并感染儿童细胞因子的差异表达。(2) 方法：对2019年作为巴基斯坦拉卡纳HIV疫情调查研究一部分招募的319名HIV阳性儿童的DNA样本进行qPCR检测，以筛查CMV和EBV。随后，分析HIV单一感染组与HIV/CMV/EBV合并感染组之间HIV病毒载量和CD4细胞计数的差异。使用RNA样本通过RT-qPCR确定单一感染组和合并感染组中促炎和抗炎细胞因子的差异表达，同时应用非配对t检验和Pearson相关检验分别分析两组中细胞因子的差异表达及相关性。(3) 结果：在319份样本中，HIV阳性儿童中活动性EBV和CMV合并感染率分别为79.9%和38.9%。HIV单一感染组与合并感染组之间的HIV病毒载量存在显著差异。在HIV单一感染组中，γ干扰素（IFN-γ）表达较低，而在其他三个合并感染组中较高。同时，在HIV单一感染组和HIV-CMV-EBV合并感染组中，转化生长因子-β1（TGF-β1）的mRNA表达较低，而在HIV-CMV和HIV-EBV合并感染组中较高。除HIV-CMV合并感染组外，IFN-γ和白细胞介素-2（IL-2）在所有组中均呈现显著正相关。(4) 结论：该研究表明，EBV/CMV合并感染的存在可影响HIV病毒载量和某些细胞因子（IFN-γ和TGF-β1）的表达，这可能影响受感染儿童的HIV疾病动态。
