Swaminathan Gokul, Navas-Martín Sonia, Martín-García Julio
Department of Microbiology and Immunology, and Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
Discov Med. 2014 Jul-Aug;18(97):15-27.
MicroRNAs (miRNAs) are important cellular, small non-coding RNAs that regulate host gene expression and have well-characterized roles in inflammation and infectious diseases. It has become apparent as well that cellular miRNAs can play crucial roles in controlling HIV-1 infection and replication. Whether HIV-1 encodes and is able to express viral miRNAs in infected cells remains controversial. HIV-1 can manipulate the biogenesis of miRNAs as well as the expression profiles of cellular miRNAs. Toll-Like receptors (TLRs) are important pathogen recognition receptors that sense invading pathogens orchestrating innate and adaptive immune responses. Innate immune recognition of HIV-1 infection leads to activation of TLR7/8. Recent evidence has shown that certain miRNAs can also be recognized by TLR7/8 leading to immune activation. However, the potential TLR7/8-mediated recognition of HIV-1 encoded miRNAs and/or cellular miRNAs modulated in HIV-1 infected cells has not been experimentally explored. In this review, we summarize the current literature on HIV-1 infection and miRNAs. Furthermore, we underscore the need for future research on potential miRNA-induced activation of TLR7/8, which might contribute to the chronic immune activation observed in HIV-1 infected patients.
微小RNA(miRNA)是重要的细胞内小非编码RNA,可调节宿主基因表达,在炎症和传染病中具有明确的作用。细胞miRNA在控制HIV-1感染和复制中也能发挥关键作用,这一点也已变得明显。HIV-1是否在感染细胞中编码并能够表达病毒miRNA仍存在争议。HIV-1可以操纵miRNA的生物合成以及细胞miRNA的表达谱。 Toll样受体(TLR)是重要的病原体识别受体,可感知入侵的病原体,协调先天免疫和适应性免疫反应。对HIV-1感染的先天免疫识别会导致TLR7/8激活。最近的证据表明,某些miRNA也可被TLR7/8识别,从而导致免疫激活。然而,尚未通过实验探索TLR7/8介导的对HIV-1编码的miRNA和/或在HIV-1感染细胞中被调节的细胞miRNA的潜在识别。在本综述中,我们总结了有关HIV-1感染和miRNA的当前文献。此外,我们强调了未来对潜在的miRNA诱导的TLR7/8激活进行研究的必要性,这可能有助于解释在HIV-1感染患者中观察到的慢性免疫激活。