Abstract
Innate immunity represents the human immune system’s first line of defense against a pathogenic intruder and is initiated by the recognition of conserved molecular structures known as pathogen-associated molecular patterns (PAMPs) by specialized cellular sensors, called pattern recognition receptors (PRRs). Human immunodeficiency virus type 1 (HIV-1) is a unique human RNA virus that causes acquired immunodeficiency syndrome (AIDS) in infected individuals. During the replication cycle, HIV-1 undergoes reverse transcription of its RNA genome and integrates the resulting DNA into the human genome. Subsequently, transcription of the integrated provirus results in production of new virions and spreading infection of the virus. Throughout the viral replication cycle, numerous nucleic acid derived PAMPs can be recognized by a diverse set of innate immune sensors in infected cells. However, HIV-1 has evolved efficient strategies to evade or counteract this immune surveillance and the downstream responses. Understanding the molecular underpinnings of the concerted actions of the innate immune system, as well as the corresponding viral evasion mechanisms during infection, is critical to understanding HIV-1 transmission and pathogenesis, and may provide important guidance for the design of appropriate adjuvant and vaccine strategies. Here, we summarize current knowledge of the molecular basis for sensing HIV-1 in human cells, including CD4+ T cells, dendritic cells, and macrophages. Furthermore, we discuss the underlying mechanisms by which innate sensing is regulated, and describe the strategies developed by HIV-1 to evade sensing and immune responses.
Highlights
Pattern recognition receptors (PRRs) act as microbial sensors for the host to initiate an immediate innate immune response through binding to invariant features of microbes, termed pathogen associated molecular patterns (PAMPs) [1,2,3]
Primary conventional dendritic cells of elite controllers mount a much more effective innate response and display greater CD8+ T-cell control of infection in comparison to cDCs from other patient groups. This response is accompanied by reduced induction of SAMHD1 in cDC from ECs, whereas TREX1 levels were significantly upregulated upon HIV exposure in cDCs from all patient groups except highly active antiretroviral therapy (HAART)-treated patients [8]
Previous studies have revealed that the innate sensing cGAS/stimulator of interferon genes (STING) pathway in antigen presenting cells (APCs) functions to augment the spontaneous generation of activated CD8+ T cells [117,118,119]
Summary
Pattern recognition receptors (PRRs) act as microbial sensors for the host to initiate an immediate innate immune response through binding to invariant features of microbes, termed pathogen associated molecular patterns (PAMPs) [1,2,3]. Once a PAMP is recognized by a PRR, a cascade of innate signaling pathways is activated, leading to induction of the host anti-viral response This includeds the secretion of interferons (IFNs), which is a potent inhibitor of a broad spectrum of viral pathogens [4,5,6]. At low multiplicity of infection (MOI), co-infection/expression of SIV virus like particles (VLPs) bearing the accessory protein Vpx, is required for detection of an innate response to HIV-1 [16,17]. The potential basis of this enhanced immunogenicity will be discussed in subsequent sections This evidence suggests that innate sensing of HIV-1 infection is likely to be a rare event, but still can have a profound impact on viral transmission and systemic pathology. A thorough understanding of the interplay between host innate immunity and HIV-1 infection will reveal mechanistic insights into HIV-1 transmission and pathogenesis, and can inform novel strategies for preventing HIV-1 infection [30,31]
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