Lazzari Elisabetta, Rozera Gabriella, Esvan Rozenn, Gagliardini Roberta, Mazzotta Valentina, Mondi Annalisa, Federici Luigi, Girardi Enrico, Antinori Andrea, Maggi Fabrizio, Abbate Isabella
Laboratory of Virology, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, 00149 Rome, Italy.
Clinical Department, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, 00149 Rome, Italy.
Int J Mol Sci. 2025 Jun 13;26(12):5673. doi: 10.3390/ijms26125673.
Human cytomegalovirus (HCMV) coinfection is associated with a faster HIV disease progression and adverse clinical outcomes. HCMV-encoded miRNA expression, in individuals acutely infected with HIV (AHI), compared to those with HCMV monoinfection, was investigated in relation to viral replication and inflammation/immune activation. Sixteen individuals with AHI coinfected with HCMV were analyzed at serodiagnosis (T0) and after 6 (T1) and 12 (T2) months of antiretroviral therapy initiated within one week from serodiagnosis. Fourteen HCMV monoinfected subjects were also studied. Plasma RNA was reverse-transcribed and amplified with a panel designed to detect 14 different HCMV-microRNAs (miRNAs). VEGF-A and IP-10 plasma levels were quantified using ELISA. Except for hcmv-miR-70-3p, detected in all subjects, hcmv-miR-UL112-3p, hcmv-miR-US25-1-5p, hcmv-miR-US25-2-3p, hcmv-miR-US4-5p, hcmv-miR-US5-1, hcmv-miR-US5-2-3p, hcmv-miR-UL36-3p, and hcmv-miR-UL36-5p were significantly more frequently detected when HCMV DNA was present (lytic infection). In latent HCMV infection, hcmv-miR-UL22A-5p and hcmv-miR-UL148D were more frequently observed in HIV/HCMV-coinfected individuals, compared to mono-HCMV infection. Hcmv-miR-UL22A-5p and hcmv-miR-US33-5p showed a direct correlation with HIV-1 RNA. Notable positive correlations between hcmv-miR-UL22A-5p and the interferon-gamma-inducible protein 10 (IP-10), as well as between hcmv-miR-UL148D and the vascular endothelial growth factor A (VEGF-A), were also observed. HCMV-miRNA expression varies between lytic and latent infection and differs in HIV coinfection. In HCMV/HIV coinfection, increased levels of hcmv-miR-UL148D, associated with VEGF-A production, seem to be less linked to HIV viremia with respect to hcmv-miR-UL22A-5p and hcmv-miR-US33-5p. A deeper understanding of HCMV-encoded miRNA biology may facilitate the comprehension of HCMV/HIV coinfection pathogenetic mechanisms.
人巨细胞病毒（HCMV）合并感染与HIV疾病进展加快及不良临床结局相关。研究了急性感染HIV（AHI）个体与HCMV单一感染个体相比，HCMV编码的miRNA表达与病毒复制及炎症/免疫激活的关系。对16例AHI合并HCMV感染的个体在血清学诊断时（T0）以及在血清学诊断后1周内开始抗逆转录病毒治疗6个月（T1）和12个月（T2）后进行分析。还研究了14例HCMV单一感染的受试者。血浆RNA经逆转录并用一组用于检测14种不同HCMV微小RNA（miRNA）的引物进行扩增。使用ELISA对血浆中血管内皮生长因子A（VEGF-A）和干扰素诱导蛋白10（IP-10）水平进行定量。除了在所有受试者中均检测到的hcmv-miR-70-3p外，当存在HCMV DNA（裂解感染）时，hcmv-miR-UL112-3p、hcmv-miR-US25-1-5p、hcmv-miR-US25-2-3p、hcmv-miR-US4-5p、hcmv-miR-US5-1、hcmv-miR-US5-2-3p、hcmv-miR-UL36-3p和hcmv-miR-UL36-5p的检测频率显著更高。在潜伏性HCMV感染中，与单一HCMV感染相比，hcmv-miR-UL22A-5p和hcmv-miR-UL148D在HIV/HCMV合并感染个体中更常被观察到。hcmv-miR-UL22A-5p和hcmv-miR-US33-5p与HIV-1 RNA呈直接相关性。还观察到hcmv-miR-UL22A-5p与干扰素-γ诱导蛋白10（IP-10）之间以及hcmv-miR-UL148D与血管内皮生长因子A（VEGF-A）之间存在显著正相关。HCMV-miRNA表达在裂解感染和潜伏感染之间有所不同，在HIV合并感染中也存在差异。在HCMV/HIV合并感染中，与VEGF-A产生相关的hcmv-miR-UL148D水平升高，相对于hcmv-miR-UL22A-5p和hcmv-miR-US33-5p，似乎与HIV病毒血症的关联较小。对HCMV编码的miRNA生物学的更深入理解可能有助于理解HCMV/HIV合并感染的发病机制。
