Downregulation of miRNA-26a by HIV-1 Enhances CD59 Expression and Packaging, Impacting Virus Susceptibility to Antibody-Dependent Complement-Mediated Lysis

被引:2
作者
Bellini, Nicolas [1 ,2 ]
Ye, Chengyu [1 ]
Ajibola, Oluwaseun [3 ]
Murooka, Thomas T. [3 ]
Lodge, Robert [1 ]
Cohen, eric A. [1 ,2 ]
机构
[1] Inst Rech Clin Montreal, Lab Human Retrovirol, Montreal, PQ H2W 1R7, Canada
[2] Univ Montreal, Fac Med, Dept Microbiol Infect Dis & Immunol, Montreal, PQ H3C 3J7, Canada
[3] Univ Manitoba, Rady Fac Hlth Sci, Dept Immunol, Winnipeg, MB R3E 0T5, Canada
来源
VIRUSES-BASEL | 2024年 / 16卷 / 07期
基金
加拿大健康研究院;
关键词
CD59; HIV-1; complement-mediated lysis; miRNA-26a; innate immunity; viral evasion; T-CELLS; NEUTRALIZING ANTIBODIES; FEEDBACK LOOP; TYPE-1; ACTIVATION; ENVELOPE; BINDING; DIFFERENTIATION; INACTIVATION; TRANSLATION;
D O I
10.3390/v16071076
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
MicroRNAs (miRNAs) play important roles in the control of HIV-1 infection. Here, we performed RNA-seq profiling of miRNAs and mRNAs expressed in CD4+ T lymphocytes upon HIV-1 infection. Our results reveal significant alterations in miRNA and mRNA expression profiles in infected relative to uninfected cells. One of the miRNAs markedly downregulated in infected cells is miRNA-26a. Among the putative targets of miRNA-26a are CD59 receptor transcripts, which are significantly upregulated in infected CD4+ T cells. The addition of miRNA-26a mimics to CD4+ T cells reduces CD59 at both the mRNA and surface protein levels, validating CD59 as a miRNA-26a target. Consistent with the reported inhibitory role of CD59 in complement-mediated lysis (CML), knocking out CD59 in CD4+ T cells renders both HIV-1-infected cells and progeny virions more prone to antibody-dependent CML (ADCML). The addition of miRNA-26a mimics to infected cells leads to enhanced sensitivity of progeny virions to ADCML, a condition linked to a reduction in CD59 packaging into released virions. Lastly, HIV-1-mediated downregulation of miRNA-26a expression is shown to be dependent on integrated HIV-1 expression but does not involve viral accessory proteins. Overall, these results highlight a novel mechanism by which HIV-1 limits ADCML by upregulating CD59 expression via miRNA-26a downmodulation.
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页数:22
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