HMGB1, an alarmin promoting HIV dissemination and latency in dendritic cells

Abstract

Dendritic cells (DCs) initiate immune responses by transporting antigens and migrating to lymphoid tissues to initiate T-cell responses. DCs are located in the mucosal surfaces that are involved in human immunodeficiency virus (HIV) transmission and they are probably among the earliest targets of HIV-1 infection. DCs have an important role in viral transmission and dissemination, and HIV-1 has evolved different strategies to evade DC antiviral activity. High mobility group box 1 (HMGB1) is a DNA-binding nuclear protein that can act as an alarmin, a danger signal to alert the innate immune system for the initiation of host defense. It is the prototypic damage-associated molecular pattern molecule, and it can be secreted by innate cells, including DCs and natural killer (NK) cells. The fate of DCs is dependent on a cognate interaction with NK cells, which involves HMGB1 expressed at NK-DC synapse. HMGB1 is essential for DC maturation, migration to lymphoid tissues and functional type-1 polarization of naïve T cells. This review highlights the latest advances in our understanding of the impact of HIV on the interactions between HMGB1 and DCs, focusing on the mechanisms of HMGB1-dependent viral dissemination and persistence in DCs, and discussing the consequences on antiviral innate immunity, immune activation and HIV pathogenesis.

Dynamic localization and the associated translocation mechanism of HMGBs in response to GCRV challenge in CIK cells

“…Nuclear-cytoplasmic translocation of HMGB1 induced by LPS has already been confirmed by numerous other studies. 8,15,27 However, among the six HMGB members, the nuclear export of only CiHMGB1b was dramatically induced by LPS stimulation in CIK cells (Figure 3c). Poly(I : C) and GCRV induced the relocation of CiHMGB1a, CiHMGB1b and CiHMGB3a from the nucleus to the cytoplasm (Figure 3a and b), which implied that a dsRNA virus or dsRNA can modulate the nucleocytoplasmic distribution of these HMGB members.…”

“…1,6 Recent discoveries illustrate that HMGBs, particularly HMGB1, function as cytokines or pro-inflammatory factors, playing a pivotal role in crosslinking innate and adaptive immunity. [7][8][9] Various studies have also highlighted the novel feature of HMGBs that function as universal sentinels for nucleic-acid-mediated innate immune responses. 7,10 Some of these studies have shown that HMGBs promiscuously recognize immunogenic nucleic acids and transduce signals to discriminate pattern recognition receptors, such as Toll-like receptors (TLRs), retinoic acid-inducible gene I-like receptors and other cytosolic receptors, to initiate the innate immune response.…”

“…13 Additionally, depending on the target cell and the microenvironment, HMGB1 may trigger or inhibit HIV-1 replication in vitro. 8 In Litopenaeus vannamei, both HMGBa and HMGBb were found to participate in the gene regulation of white spot syndrome virus. 14 In grass carp, the antiviral activities of all six HMGBs (CiHMGB1a, CiHMGB1b, CiHMGB2a, CiHMGB2b, CiHMGB3a and CiHMGB3b) have been investigated in response to grass carp reovirus (GCRV) and all of them participate in triggering immune signaling pathways.…”

“…7 Serving as classical nuclear localization proteins to function as cytokines or sentinels for innate immune responses, HMGBs must shuttle from the nucleus to the cytoplasm or be released into the extracellular milieu to trigger the activation of transmembrane and cytosolic receptors. 8 Therefore, there is an urgent need to identify the induction and regulation mechanisms of the nucleocytoplasmic distribution of HMGBs. Although some evidence has revealed that HMGBs can shuttle from the nucleus to the cytoplasm through the stimulation of a microbial component or be released to the extracellular environment by dead and dying cells, these studies have mainly focused on mammalian HMGB1.…”

HMGB1 Promotes Hepatitis C Virus Replication by Interaction with Stem-Loop 4 in the Viral 5′ Untranslated Region

“…HMGB1 was shown to be released from cells infected with a range of viruses, including dengue virus, HCV, and human immunodeficiency virus (HIV) (34)(35)(36)(37). Although a recent study suggested that HMGB1 released from virus-infected cells could block HCV infection, the role of intracellular HMGB1 in HCV replication and/or translation is still unclear (35).…”