The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
HIV-1 infection and AIDS dementia are influenced by a mutant MCP-1 allele linked to increased monocyte infiltration of tissues and MCP-1 levels
Open accessAbstract
Studies in humans and in experimental models of HIV-1 infection indicate an important role for monocyte chemoattractant protein-1 (MCP-1; also known as CC chemokine ligand 2), a potent chemoattractant and activator of mononuclear phagocytes (MP) in the pathogenesis of HIV-associated dementia (HAD). We determined the influence of genetic variation in MCP-1 on HIV-1 pathogenesis in large cohorts of HIV-1-infected adults and children. In adults, homozygosity for the MCP-1–2578G allele was associated with a 50% reduction in the risk of acquiring HIV-1. However, once HIV-1 infection was established, this same MCP-1 genotype was associated with accelerated disease progression and a 4.5-fold increased risk of HAD. We examined the molecular and cellular basis for these genotype–phenotype associations and found that the mutant MCP-1–2578G allele conferred greater transcriptional activity via differential DNA–protein interactions, enhanced protein production in vitro, increased serum MCP-1 levels, as well as MP infiltration into tissues. Thus, MCP-1 expression had a two-edged role in HIV-1 infection: it afforded partial protection from viral infection, but during infection, its proinflammatory properties and ability to up-regulate HIV-1 replication collectively may contribute to accelerated disease progression and increased risk of dementia. Our findings suggest that MCP-1 antagonists may be useful in HIV-1 infection, especially for HAD, and that HIV+ individuals possessing the MCP-1–2578G allele may benefit from early initiation of antiretroviral drugs that effectively cross the blood–brain barrier. In a broader context, the MCP-1–2578G allele may serve as a genetic determinant of outcome of other disease states in which MP-mediated tissue injury is central to disease pathogenesis.
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Cites
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Cited by
Monocyte Chemoattractant Protein-1 (MCP-1): An Overview
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Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function
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Neurological complications of HIV infection
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Metadata
- Authors
- Gonzalez, E., Rovin, B. H., Sen, L., Cooke, G., Dhanda, R., Mummidi, S., Kulkarni, H., Bamshad, M. J., Telles, V., Anderson, S. A., Walter, E. A., Stephan, K. T., Deucher, M., Mangano, A., Bologna, R., Ahuja, S. S., Dolan, M. J., & Ahuja, S. K.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2002-10-08
- Volume
- 99
- Issue
- 21
- Pages
- 13795-13800
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2026924553
- Cited by
- 302
- References
- 42
- FWCI
- 5.17
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: HIV-1 infection and AIDS dementia are influenced by a mutant MCP-1 allele linked to increased monocyte infiltration of tissues and MCP-1 levels. https://app.cochat.ai/papers/10.1073/pnas.202357499
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- Gonzalez, E., Rovin, B. H., Sen, L., Cooke, G., Dhanda, R., Mummidi, S., Kulkarni, H., Bamshad, M. J., Telles, V., Anderson, S. A., Walter, E. A., Stephan, K. T., Deucher, M., Mangano, A., Bologna, R., Ahuja, S. S., Dolan, M. J., & Ahuja, S. K. (2002). HIV-1 infection and AIDS dementia are influenced by a mutant MCP-1 allele linked to increased monocyte infiltration of tissues and MCP-1 levels. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.202357499
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
