Naturally Occurring Deletional Mutation in the C-terminal Cytoplasmic Tail of CCR5 Affects Surface Trafficking of CCR5

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2001 Mar 10

PMID 11238872

Citations 17

Authors

T Shioda

E E Nakayama

Y Tanaka

X Xin

H Liu

A Kato

Y Sakai

Y Nagai

A Iwamoto

Affiliations

Soon will be listed here.

Abstract

CCR5 is an essential coreceptor for the cellular entry of R5 strains of human immunodeficiency virus type 1 (HIV-1). CCR5-893(-) is a single-nucleotide deletion mutation which is observed exclusively in Asians (M. A. Ansari-Lari, et al., Nat. Genet. 16:221-222, 1997). This mutant gene produces a CCR5 which lacks the entire C-terminal cytoplasmic tail. To assess the effect of CCR5-893(-) on HIV-1 infection, we generated a recombinant Sendai virus expressing the mutant CCR5 and compared its HIV-1 coreceptor activity with that of wild-type CCR5. Although the mutant CCR5 has intact extracellular domains, its coreceptor activity was much less than that of wild-type CCR5. Flow cytometric analyses and confocal microscopic observation of cells expressing the mutant CCR5 revealed that surface CCR5 levels were greatly reduced in these cells, while cytoplasmic CCR5 levels of the mutant CCR5 were comparable to that of the wild type. Peripheral blood CD4(+) T cells obtained from individuals heterozygous for this allele expressed very low levels of CCR5. These data suggest that the CCR5-893(-) mutation affects intracellular transport of CCR5 and raise the possibility that this mutation also affects HIV-1 transmission and disease progression.

Citing Articles

Control of CCR5 Cell-Surface Targeting by the PRAF2 Gatekeeper.

Da Silva E, Scott M, Enslen H, Marullo S Int J Mol Sci. 2023; 24(24).

PMID: 38139265 PMC: 10744302. DOI: 10.3390/ijms242417438.

Higher Infectivity of the Human Immunodeficiency Virus in Sensitive Cells with a Modification of the CCR5 Gene.

Nosik D, Kalnina L, Selimova L, Pronin A Dokl Biol Sci. 2023; 511(1):251-254.

PMID: 37833581 DOI: 10.1134/S0012496623700412.

Predominance of the heterozygous CCR5 delta-24 deletion in African individuals resistant to HIV infection might be related to a defect in CCR5 addressing at the cell surface.

Arendt V, Amand M, Iserentant G, Lemaire M, Masquelier C, Ndayisaba G J Int AIDS Soc. 2019; 22(9):e25384.

PMID: 31486251 PMC: 6727025. DOI: 10.1002/jia2.25384.

CCR5 promoter haplotypes differentially influence CCR5 expression on natural killer and T cell subsets in ethnically divergent HIV-1 uninfected South African populations.

Picton A, Paximadis M, Tiemessen C Immunogenetics. 2012; 64(11):795-806.

PMID: 22893032 DOI: 10.1007/s00251-012-0642-0.

CXCR1 as a novel target for directing reactive T cells toward melanoma: implications for adoptive cell transfer immunotherapy.

Sapoznik S, Ortenberg R, Galore-Haskel G, Kozlovski S, Levy D, Avivi C Cancer Immunol Immunother. 2012; 61(10):1833-47.

PMID: 22441657 PMC: 11028868. DOI: 10.1007/s00262-012-1245-1.

References

Kostrikis L, Huang Y, Moore J, Wolinsky S, Zhang L, Guo Y . A chemokine receptor CCR2 allele delays HIV-1 disease progression and is associated with a CCR5 promoter mutation. Nat Med. 1998; 4(3):350-3. DOI: 10.1038/nm0398-350. View

Ruffing N, Sullivan N, Sharmeen L, Sodroski J, Wu L . CCR5 has an expanded ligand-binding repertoire and is the primary receptor used by MCP-2 on activated T cells. Cell Immunol. 1998; 189(2):160-8. DOI: 10.1006/cimm.1998.1379. View

Hu H, Shioda T, Hori T, Moriya C, Kato A, Sakai Y . Dissociation of ligand-induced internalization of CXCR-4 from its co-receptor activity for HIV-1 Env-mediated membrane fusion. Arch Virol. 1998; 143(5):851-61. DOI: 10.1007/s007050050337. View

van Rij R, Broersen S, Goudsmit J, Coutinho R, Schuitemaker H . The role of a stromal cell-derived factor-1 chemokine gene variant in the clinical course of HIV-1 infection. AIDS. 1998; 12(9):F85-90. View

Lalani A, Masters J, Zeng W, Barrett J, Pannu R, Everett H . Use of chemokine receptors by poxviruses. Science. 1999; 286(5446):1968-71. DOI: 10.1126/science.286.5446.1968. View

Sellebjerg F, Madsen H, Jensen C, Jensen J, Garred P . CCR5 delta32, matrix metalloproteinase-9 and disease activity in multiple sclerosis. J Neuroimmunol. 2000; 102(1):98-106. DOI: 10.1016/s0165-5728(99)00166-6. View

Ohagen A, Li L, Rosenzweig A, Gabuzda D . Cell-dependent mechanisms restrict the HIV type 1 coreceptor activity of US28, a chemokine receptor homolog encoded by human cytomegalovirus. AIDS Res Hum Retroviruses. 2000; 16(1):27-35. DOI: 10.1089/088922200309575. View

Reynes J, Portales P, Segondy M, Baillat V, Andre P, Reant B . CD4+ T cell surface CCR5 density as a determining factor of virus load in persons infected with human immunodeficiency virus type 1. J Infect Dis. 2000; 181(3):927-32. DOI: 10.1086/315315. View

Magierowska M, Lepage V, Lien T, Lan N, Guillotel M, Issafras H . Novel variant of the CCR5 gene in a Vietnamese population. Microbes Infect. 2000; 1(2):123-4. DOI: 10.1016/s1286-4579(99)80002-1. View

10.

Asjo B, Albert J, Biberfeld G, Karlsson A, Lidman K, Fenyo E . Replicative capacity of human immunodeficiency virus from patients with varying severity of HIV infection. Lancet. 1986; 2(8508):660-2. View

11.

Cheng-Mayer C, Seto D, Tateno M, Levy J . Biologic features of HIV-1 that correlate with virulence in the host. Science. 1988; 240(4848):80-2. DOI: 10.1126/science.2832945. View

12.

Tersmette M, Lange J, de Goede R, de Wolf F, Schellekens P, Coutinho R . Association between biological properties of human immunodeficiency virus variants and risk for AIDS and AIDS mortality. Lancet. 1989; 1(8645):983-5. DOI: 10.1016/s0140-6736(89)92628-7. View

13.

Shioda T, Shibuta H . Production of human immunodeficiency virus (HIV)-like particles from cells infected with recombinant vaccinia viruses carrying the gag gene of HIV. Virology. 1990; 175(1):139-48. DOI: 10.1016/0042-6822(90)90194-v. View

14.

Connor R, Mohri H, Cao Y, Ho D . Increased viral burden and cytopathicity correlate temporally with CD4+ T-lymphocyte decline and clinical progression in human immunodeficiency virus type 1-infected individuals. J Virol. 1993; 67(4):1772-7. PMC: 240220. DOI: 10.1128/JVI.67.4.1772-1777.1993. View

15.

Zhu T, Mo H, Wang N, Nam D, Cao Y, Koup R . Genotypic and phenotypic characterization of HIV-1 patients with primary infection. Science. 1993; 261(5125):1179-81. DOI: 10.1126/science.8356453. View

16.

Charo I, Myers S, Herman A, Franci C, Connolly A, Coughlin S . Molecular cloning and functional expression of two monocyte chemoattractant protein 1 receptors reveals alternative splicing of the carboxyl-terminal tails. Proc Natl Acad Sci U S A. 1994; 91(7):2752-6. PMC: 43448. DOI: 10.1073/pnas.91.7.2752. View

17.

Nussbaum O, Broder C, BERGER E . Fusogenic mechanisms of enveloped-virus glycoproteins analyzed by a novel recombinant vaccinia virus-based assay quantitating cell fusion-dependent reporter gene activation. J Virol. 1994; 68(9):5411-22. PMC: 236941. DOI: 10.1128/JVI.68.9.5411-5422.1994. View

18.

Cocchi F, Devico A, Garzino-Demo A, Arya S, Gallo R, Lusso P . Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells. Science. 1995; 270(5243):1811-5. DOI: 10.1126/science.270.5243.1811. View

19.

Feng Y, Broder C, Kennedy P, BERGER E . HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science. 1996; 272(5263):872-7. DOI: 10.1126/science.272.5263.872. View

20.

Deng H, Liu R, Ellmeier W, Choe S, Unutmaz D, Burkhart M . Identification of a major co-receptor for primary isolates of HIV-1. Nature. 1996; 381(6584):661-6. DOI: 10.1038/381661a0. View