HIV-1 Envelope-receptor Interactions Required for Macrophage Infection and Implications for Current HIV-1 Cure Strategies

Overview

Journal J Leukoc Biol

Publisher Oxford University Press

Specialty Allergy & Immunology

Date 2013 Oct 26

PMID 24158961

Citations 22

Authors

Paul R Gorry

Nicholas Francella

Sharon R Lewin

Ronald G Collman

Affiliations

Soon will be listed here.

Abstract

Myeloid cells residing in the CNS and lymphoid tissues are targets for productive HIV-1 replication, and their infection contributes to the pathological manifestations of HIV-1 infection. The Envs can adopt altered configurations to overcome entry restrictions in macrophages via a more efficient and/or altered mechanism of engagement with cellular receptors. This review highlights evidence supporting an important role for macrophages in HIV-1 pathogenesis and persistence, which need to be considered for strategies aimed at achieving a functional or sterilizing cure. We also highlight that the molecular mechanisms underlying HIV-1 tropism for macrophages are complex, involving enhanced and/or altered interactions with CD4, CCR5, and/or CXCR4, and that the nature of these interactions may depend on the anatomical location of the virus.

Citing Articles

Macrophages: Key Cellular Players in HIV Infection and Pathogenesis.

Woottum M, Yan S, Sayettat S, Grinberg S, Cathelin D, Bekaddour N Viruses. 2024; 16(2).

PMID: 38400063 PMC: 10893316. DOI: 10.3390/v16020288.

A high-throughput screening assay for silencing established HIV-1 macrophage infection identifies nucleoside analogs that perturb H3K9me3 on proviral genomes.

Yi Y, Zankharia U, Cassel J, Lu F, Salvino J, Lieberman P J Virol. 2023; 97(8):e0065323.

PMID: 37578230 PMC: 10506489. DOI: 10.1128/jvi.00653-23.

Animal models for studies of HIV-1 brain reservoirs.

Waight E, Zhang C, Mathews S, Kevadiya B, Lloyd K, Gendelman H J Leukoc Biol. 2022; 112(5):1285-1295.

PMID: 36044375 PMC: 9804185. DOI: 10.1002/JLB.5VMR0322-161R.

Characterization of Macrophage-Tropic HIV-1 Infection of Central Nervous System Cells and the Influence of Inflammation.

Woodburn B, Kanchi K, Zhou S, Colaianni N, Joseph S, Swanstrom R J Virol. 2022; 96(17):e0095722.

PMID: 35975998 PMC: 9472603. DOI: 10.1128/jvi.00957-22.

Dopamine Levels Induced by Substance Abuse Alter Efficacy of Maraviroc and Expression of CCR5 Conformations on Myeloid Cells: Implications for NeuroHIV.

Matt S, Nickoloff-Bybel E, Rong Y, Runner K, Johnson H, OConnor M Front Immunol. 2021; 12:663061.

PMID: 34093554 PMC: 8170305. DOI: 10.3389/fimmu.2021.663061.

References

Croul S, Sverstiuk A, Capini C, LHeureux D, Regulier E, Richardson M . CNS invasion by CD14+/CD16+ peripheral blood-derived monocytes in HIV dementia: perivascular accumulation and reservoir of HIV infection. J Neurovirol. 2001; 7(6):528-41. DOI: 10.1080/135502801753248114. View

Ping L, Joseph S, Anderson J, Abrahams M, Salazar-Gonzalez J, Kincer L . Comparison of viral Env proteins from acute and chronic infections with subtype C human immunodeficiency virus type 1 identifies differences in glycosylation and CCR5 utilization and suggests a new strategy for immunogen design. J Virol. 2013; 87(13):7218-33. PMC: 3700278. DOI: 10.1128/JVI.03577-12. View

Peters P, Duenas-Decamp M, Sullivan W, Brown R, Ankghuambom C, Luzuriaga K . Variation in HIV-1 R5 macrophage-tropism correlates with sensitivity to reagents that block envelope: CD4 interactions but not with sensitivity to other entry inhibitors. Retrovirology. 2008; 5:5. PMC: 2268948. DOI: 10.1186/1742-4690-5-5. View

Collman R, Balliet J, Gregory S, Friedman H, Kolson D, NATHANSON N . An infectious molecular clone of an unusual macrophage-tropic and highly cytopathic strain of human immunodeficiency virus type 1. J Virol. 1992; 66(12):7517-21. PMC: 240461. DOI: 10.1128/JVI.66.12.7517-7521.1992. View

Steffens C, Hope T . Mobility of the human immunodeficiency virus (HIV) receptor CD4 and coreceptor CCR5 in living cells: implications for HIV fusion and entry events. J Virol. 2004; 78(17):9573-8. PMC: 506925. DOI: 10.1128/JVI.78.17.9573-9578.2004. View

Koppensteiner H, Brack-Werner R, Schindler M . Macrophages and their relevance in Human Immunodeficiency Virus Type I infection. Retrovirology. 2012; 9:82. PMC: 3484033. DOI: 10.1186/1742-4690-9-82. View

Vandekerckhove L, Wensing A, Kaiser R, Brun-Vezinet F, Clotet B, De Luca A . European guidelines on the clinical management of HIV-1 tropism testing. Lancet Infect Dis. 2011; 11(5):394-407. DOI: 10.1016/S1473-3099(10)70319-4. View

Goodenow M, Collman R . HIV-1 coreceptor preference is distinct from target cell tropism: a dual-parameter nomenclature to define viral phenotypes. J Leukoc Biol. 2006; 80(5):965-72. DOI: 10.1189/jlb.0306148. View

Martin J, LaBranche C . Differential CD4/CCR5 utilization, gp120 conformation, and neutralization sensitivity between envelopes from a microglia-adapted human immunodeficiency virus type 1 and its parental isolate. J Virol. 2001; 75(8):3568-80. PMC: 114848. DOI: 10.1128/JVI.75.8.3568-3580.2001. View

10.

Poveda E, Alcami J, Paredes R, Cordoba J, Gutierrez F, Llibre J . Genotypic determination of HIV tropism - clinical and methodological recommendations to guide the therapeutic use of CCR5 antagonists. AIDS Rev. 2010; 12(3):135-48. View

11.

Yi Y, Shaheen F, Collman R . Preferential use of CXCR4 by R5X4 human immunodeficiency virus type 1 isolates for infection of primary lymphocytes. J Virol. 2005; 79(3):1480-6. PMC: 544090. DOI: 10.1128/JVI.79.3.1480-1486.2005. View

12.

Alkhatib G, Combadiere C, Broder C, Feng Y, Kennedy P, Murphy P . CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macrophage-tropic HIV-1. Science. 1996; 272(5270):1955-8. DOI: 10.1126/science.272.5270.1955. View

13.

Lawn S, Roberts B, Griffin G, Folks T, Butera S . Cellular compartments of human immunodeficiency virus type 1 replication in vivo: determination by presence of virion-associated host proteins and impact of opportunistic infection. J Virol. 1999; 74(1):139-45. PMC: 111522. View

14.

Roche M, Salimi H, Duncan R, Wilkinson B, Chikere K, Moore M . A common mechanism of clinical HIV-1 resistance to the CCR5 antagonist maraviroc despite divergent resistance levels and lack of common gp120 resistance mutations. Retrovirology. 2013; 10:43. PMC: 3648390. DOI: 10.1186/1742-4690-10-43. View

15.

Gonzalez-Scarano F, Martin-Garcia J . The neuropathogenesis of AIDS. Nat Rev Immunol. 2005; 5(1):69-81. DOI: 10.1038/nri1527. View

16.

Hutter G, Nowak D, Mossner M, Ganepola S, Mussig A, Allers K . Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. N Engl J Med. 2009; 360(7):692-8. DOI: 10.1056/NEJMoa0802905. View

17.

Triques K, Stevenson M . Characterization of restrictions to human immunodeficiency virus type 1 infection of monocytes. J Virol. 2004; 78(10):5523-7. PMC: 400363. DOI: 10.1128/jvi.78.10.5523-5527.2004. View

18.

Musich T, Peters P, Duenas-Decamp M, Gonzalez-Perez M, Robinson J, Zolla-Pazner S . A conserved determinant in the V1 loop of HIV-1 modulates the V3 loop to prime low CD4 use and macrophage infection. J Virol. 2010; 85(5):2397-405. PMC: 3067776. DOI: 10.1128/JVI.02187-10. View

19.

Dalgleish A, Beverley P, Clapham P, Crawford D, Greaves M, Weiss R . The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature. 1984; 312(5996):763-7. DOI: 10.1038/312763a0. View

20.

Allers K, Hutter G, Hofmann J, Loddenkemper C, Rieger K, Thiel E . Evidence for the cure of HIV infection by CCR5Δ32/Δ32 stem cell transplantation. Blood. 2010; 117(10):2791-9. DOI: 10.1182/blood-2010-09-309591. View