ArticleThe Journal of biological chemistry2011
LIM kinase 1 modulates cortical actin and CXCR4 cycling and is activated by HIV-1 to initiate viral infection.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 102 citations in OpenAlex.
- Cofilin hyperactivation in HIV infection and targeting the cofilin pathway using an anti-αScience advances · 2019Trial
- Trial
- A dichotomy in cortical actin and chemotactic actin activity between human memory and naive T cells contributes to their differential susceptibility to HIV-1 infection.The Journal of biological chemistry · 2012Trial
- Discovery of actinators, actin-derived bioactive peptides that modulate cytoskeleton and actin-related cellular activities.Science advances · 2026Article
- HSV-1 infection induces brain cofilin hyperphosphorylation in the 5×FAD Alzheimer's Disease mouse model.bioRxiv : the preprint server for biology · 2025Article
- Rottlerin inhibits macropinocytosis of Porcine Reproductive and Respiratory Syndrome Virus through the PKCδ-Cofilin signaling pathway.PloS one · 2025Article
- Characterization of a CXCR4 antagonist TIQ-15 with dual tropic HIV entry inhibition properties.PLoS pathogens · 2024Article
- RNA-RNA interactions between respiratory syncytial virus and miR-26 and miR-27 are associated with regulation of cell cycle and antiviral immunity.Nucleic acids research · 2024Article
- The host cytoskeleton: a key regulator of early HIV-1 infection.The FEBS journal · 2024Review
- α-Synuclein triggers cofilin pathology and dendritic spine impairment via a PrPCell death & disease · 2024Article
- Effects of polybrene and retronectin as transduction enhancers on the development and phenotypic characteristics of VHH-based CD19-redirected CAR T cells: a comparative investigation.Clinical and experimental medicine · 2023Article
- Role of ROCK signaling in virus replication.Virus research · 2023Review
- The Antiviral Compound PSP Inhibits HIV-1 Entry via PKR-Dependent Activation in Monocytic Cells.Viruses · 2023Article
- LIM Kinases, LIMK1 and LIMK2, Are Crucial Node Actors of the Cell Fate: Molecular to Pathological Features.Cells · 2023Review
- Advances in the Development of Small Molecule Antivirals against Equine Encephalitic Viruses.Viruses · 2023Review
- Estradiol inhibits HIV-1Scientific reports · 2022Article
- A Progressive Loss of phosphoSer138-Profilin Aligns with Symptomatic Course in the R6/2 Mouse Model of Huntington's Disease: Possible Sex-Dependent Signaling.Cellular and molecular neurobiology · 2022Article
- CounterAKTing HIV: Toward a "Block and Clear" Strategy?Frontiers in cellular and infection microbiology · 2022Review
- Prestimulation of CD2 confers resistance to HIV-1 latent infection in blood resting CD4 T cells.iScience · 2021Article
- Co-receptor signaling in the pathogenesis of neuroHIV.Retrovirology · 2021Review
6 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Almost all viral pathogens utilize a cytoskeleton for their entry and intracellular transport. In HIV-1 infection, binding of the virus to blood resting CD4 T cells initiates a temporal course of cortical actin polymerization and depolymerization, a process mimicking the chemotactic response initiated from chemokine receptors. The actin depolymerization has been suggested to promote viral intracellular migration through cofilin-mediated actin treadmilling. However, the role of the virus-mediated actin polymerization in HIV infection is unknown, and the signaling molecules involved remain unidentified. Here we describe a pathogenic mechanism for triggering early actin polymerization through HIV-1 envelope-mediated transient activation of the LIM domain kinase (LIMK), a protein that phosphorylates cofilin. We demonstrate that HIV-mediated LIMK activation is through gp120-triggered transient activation of the Rack-PAK-LIMK pathway, and that knockdown of LIMK through siRNA decreases filamentous actin, increases CXCR4 trafficking, and diminishes viral DNA synthesis. These results suggest that HIV-mediated early actin polymerization may directly regulate the CXCR4 receptor during viral entry and is involved in viral DNA synthesis. Furthermore, we also demonstrate that in resting CD4 T cells, actin polymerization can be triggered through transient treatment with a pharmacological agent, okadaic acid, that activates LIMK and promotes HIV latent infection of resting CD4 T cells. Taken together, our results suggest that HIV hijacks LIMK to control the cortical actin dynamics for the initiation of viral infection of CD4 T cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.