Interplay between Intrinsic and Innate Immunity during HIV Infection

Bergantz, Louis; Subra, Frédéric; Deprez, Eric; Delelis, Olivier; Richetta, Clémence

doi:10.3390/cells8080922

Cited by 30 publications

(37 citation statements)

References 288 publications

(379 reference statements)

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“…Several genes have been identified as encoding potential PRRs for retroviruses, and the overall diversity of retrovirus PRRs has been reviewed elsewhere [ 39 , 40 , 41 ]. These studies have revealed a diverse set of retrovirus sensing pathways that respond to a variety of retrovirus-associated molecules–including both viral genomic RNA, reverse transcribed viral DNA, viral proteins, as well as non-viral molecules associated with retroviral particles.…”

Section: Innate Sensing Receptors For Retrovirusesmentioning

confidence: 99%

The Role of Toll-Like Receptors in Retroviral Infection

Browne

2020

Microorganisms

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Toll-like receptors (TLRs) are key pathogen sensing receptors that respond to diverse microbial ligands, and trigger both innate and adaptive immune responses to infection. Since their discovery, a growing body of evidence has pointed to an important role for TLRs in retroviral infection and pathogenesis. These data suggest that multiple TLRs contribute to the anti-retroviral response, and that TLR engagement by retroviruses can have complex and divergent outcomes for infection. Despite this progress, numerous questions remain about the role of TLRs in retroviral infection. In this review, I summarize existing evidence for TLR-retrovirus interactions and the functional roles these receptors play in immunity and pathogenesis, with particular focus on human immunodeficiency virus (HIV).

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Section: Innate Sensing Receptors For Retrovirusesmentioning

confidence: 99%

The Role of Toll-Like Receptors in Retroviral Infection

Browne

2020

Microorganisms

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“…In addition to providing a first line of defence against pathogen infection, innate immune responses are pivotal in priming the adaptive immune responses through the induction of antigen specific T cell activation and promotion of humoral immunity. Thus, understanding mechanisms by which the innate immune system recognizes and responds to HIV will be instructive in the design of HIV-1 vaccines and/or adjuvants [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

“…To date, multiple families of PRRs have been implicated as sensors responsible for detecting HIV-1 infection, which include toll-like receptors (TLRs), RIG-I-like receptors (RLRs), and cytosolic DNA sensors (Table 1) [16,[22][23][24]. The mechanistic details for initiation and regulation of HIV-1 innate sensing have been extensively studied, but remain controversial regarding the PAMP, innate sensors, and regulators involved in physiologically-relevant sensing processes [9,10,25]. Moreover, HIV-1 has evolved elaborate strategies to circumvent immune surveillance and response.…”

Section: Introductionmentioning

confidence: 99%

Sensor Sensibility—HIV-1 and the Innate Immune Response

Yin

Langer

Zhang

et al. 2020

Cells

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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.

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“…These have been termed restriction factors and constitute the so-called intrinsic immunity, which is now considered to be the third arm of immunity [ 1 ]. Most restriction factors, however, even if they are constitutively expressed, are upregulated by type I interferon(s), and thus intrinsic defenses can be considered to be a part of antiviral innate immunity [ 2 , 3 ]. Since the discovery of the first HIV-1 restriction factor, in 2002, APOBEC3G [ 4 ], many other factors have been identified and shown to inhibit nearly all steps of the HIV-1 replicative cycle (reviewed in [ 5 , 6 , 7 ]).…”

Section: Introductionmentioning

confidence: 99%

Daxx Inhibits HIV-1 Reverse Transcription and Uncoating in a SUMO-Dependent Manner

Maillet

Fernandez

Decourcelle

et al. 2020

Viruses

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Death domain-associated protein 6 (Daxx) is a multifunctional, ubiquitously expressed and highly conserved chaperone protein involved in numerous cellular processes, including apoptosis, transcriptional repression, and carcinogenesis. In 2015, we identified Daxx as an antiretroviral factor that interfered with HIV-1 replication by inhibiting the reverse transcription step. In the present study, we sought to unravel the molecular mechanism of Daxx-mediated restriction and, in particular, to identify the protein(s) that Daxx targets in order to achieve its antiviral activity. First, we show that the SUMO-interacting motif (SIM) located at the C-terminus of the protein is strictly required for Daxx to inhibit HIV-1 reverse transcription. By performing a quantitative proteomic screen combined with classical biochemical analyses, we found that Daxx associated with incoming HIV-1 cores through a SIM-dependent interaction with cyclophilin A (CypA) and capsid (CA). Daxx was found to reside within a multiprotein complex associated with viral capsids, also containing TNPO3, TRIM5α, and TRIM34. Given the well-known influence of these cellular factors on the stability of HIV-1 cores, we investigated the effect of Daxx on the cytoplasmic fate of incoming cores and found that Daxx prevented HIV-1 uncoating in a SIM-dependent manner. Altogether, our findings suggest that, by recruiting TNPO3, TRIM5α, and TRIM34 and possibly other proteins onto incoming HIV-1 cores through a SIM-dependent interaction with CA-bound CypA, Daxx increases their stability, thus preventing uncoating and reverse transcription. Our study uncovers a previously unknown function of Daxx in the early steps of HIV-1 infection and further illustrates how reverse transcription and uncoating are two tightly interdependent processes.

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Interplay between Intrinsic and Innate Immunity during HIV Infection

Cited by 30 publications

References 288 publications

The Role of Toll-Like Receptors in Retroviral Infection

The Role of Toll-Like Receptors in Retroviral Infection

Sensor Sensibility—HIV-1 and the Innate Immune Response

Daxx Inhibits HIV-1 Reverse Transcription and Uncoating in a SUMO-Dependent Manner

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