CCL3L1 and CCR5 influence cell-mediated immunity and affect HIV-AIDS pathogenesis via viral entry-independent mechanisms

Matthew J. Dolan; Hemant Kulkarni; Jose F. Camargo; Weijing He; Alison Smith; Juan Manuel Anaya; Toshiyuki Miura; Frederick M. Hecht; Manju Mamtani; Florencia Pereyra; Vincent Marconi; Andrea Mangano; Luisa Sen; Rosa Bologna; Robert A. Clark; Stephanie A. Anderson; Judith Delmar; Robert J. O'Connell; Andrew Lloyd; Jeffrey Martin; Seema S. Ahuja; Brian K. Agan; Bruce D. Walker; Steven G. Deeks; Sunil K. Ahuja

doi:10.1038/ni1521

CCL3L1 and CCR5 influence cell-mediated immunity and affect HIV-AIDS pathogenesis via viral entry-independent mechanisms

Matthew J. Dolan, Hemant Kulkarni, Jose F. Camargo, Weijing He, Alison Smith, Juan Manuel Anaya, Toshiyuki Miura, Frederick M. Hecht, Manju Mamtani, Florencia Pereyra, Vincent Marconi, Andrea Mangano, Luisa Sen, Rosa Bologna, Robert A. Clark, Stephanie A. Anderson, Judith Delmar, Robert J. O'Connell, Andrew Lloyd, Jeffrey MartinSeema S. Ahuja, Brian K. Agan, Bruce D. Walker, Steven G. Deeks, Sunil K. Ahuja

urosario

Research output: Contribution to journal › Research Article › peer-review

151 Scopus citations

Abstract

Although host defense against human immunodeficiency virus 1 (HIV-1) relies mainly on cell-mediated immunity (CMI), the determinants of CMI in humans are poorly understood. Here we demonstrate that variations in the genes encoding the chemokine CCL3L1 and HIV coreceptor CCR5 influence CMI in both healthy and HIV-infected individuals. CCL3L1-CCR5 genotypes associated with altered CMI in healthy subjects were similar to those that influence the risk of HIV transmission, viral burden and disease progression. However, CCL3L1-CCR5 genotypes also modify HIV clinical course independently of their effects on viral load and CMI. These results identify CCL3L1 and CCR5 as major determinants of CMI and demonstrate that these host factors influence HIV pathogenesis through their effects on both CMI and other viral entry-independent mechanisms.

Original language	English (US)
Pages (from-to)	1324-1336
Number of pages	13
Journal	Nature Immunology
Volume	8
Issue number	12
DOIs	https://doi.org/10.1038/ni1521
State	Published - Dec 2007

All Science Journal Classification (ASJC) codes

Immunology and Allergy
Immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/ni1521

Cite this

Dolan, M. J., Kulkarni, H., Camargo, J. F., He, W., Smith, A., Anaya, J. M., Miura, T., Hecht, F. M., Mamtani, M., Pereyra, F., Marconi, V., Mangano, A., Sen, L., Bologna, R., Clark, R. A., Anderson, S. A., Delmar, J., O'Connell, R. J., Lloyd, A., ... Ahuja, S. K. (2007). CCL3L1 and CCR5 influence cell-mediated immunity and affect HIV-AIDS pathogenesis via viral entry-independent mechanisms. Nature Immunology, 8(12), 1324-1336. https://doi.org/10.1038/ni1521

@article{408c58182a73408388daed66e4205cd3,

title = "CCL3L1 and CCR5 influence cell-mediated immunity and affect HIV-AIDS pathogenesis via viral entry-independent mechanisms",

abstract = "Although host defense against human immunodeficiency virus 1 (HIV-1) relies mainly on cell-mediated immunity (CMI), the determinants of CMI in humans are poorly understood. Here we demonstrate that variations in the genes encoding the chemokine CCL3L1 and HIV coreceptor CCR5 influence CMI in both healthy and HIV-infected individuals. CCL3L1-CCR5 genotypes associated with altered CMI in healthy subjects were similar to those that influence the risk of HIV transmission, viral burden and disease progression. However, CCL3L1-CCR5 genotypes also modify HIV clinical course independently of their effects on viral load and CMI. These results identify CCL3L1 and CCR5 as major determinants of CMI and demonstrate that these host factors influence HIV pathogenesis through their effects on both CMI and other viral entry-independent mechanisms.",

author = "Dolan, {Matthew J.} and Hemant Kulkarni and Camargo, {Jose F.} and Weijing He and Alison Smith and Anaya, {Juan Manuel} and Toshiyuki Miura and Hecht, {Frederick M.} and Manju Mamtani and Florencia Pereyra and Vincent Marconi and Andrea Mangano and Luisa Sen and Rosa Bologna and Clark, {Robert A.} and Anderson, {Stephanie A.} and Judith Delmar and O'Connell, {Robert J.} and Andrew Lloyd and Jeffrey Martin and Ahuja, {Seema S.} and Agan, {Brian K.} and Walker, {Bruce D.} and Deeks, {Steven G.} and Ahuja, {Sunil K.}",

note = "Funding Information: 1Infectious Disease Clinical Research Program, 2Infectious Diseases Service and 3Henry M. Jackson Foundation, Wilford Hall United States Air Force Medical Center, Lackland Air Force Base, Texas 78236, USA. 4Veterans Administration Research Center for AIDS and HIV-1 Infection, South Texas Veterans Health Care System, and Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA. 5School of Psychology, University of Western Sydney, PenrithSth,NewSouthWales1797,Australia.6CellularBiologyandImmunogeneticsUnit,Corporaci{\'o}nparaInvestigacionesBiologicas–UniversityofRosario,Cra7278-B-141, Medellin, Colombia. 7Partners AIDS Research Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. 8Division of AIDS, Harvard Medical School, Boston, Massachusetts 02114, USA. 9Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA. 10Department of Medicine, University of California, and San Francisco General Hospital, San Francisco, California 94110, USA. 11Laboratorio de Biolog{\'i}a Celular y Retrovirus, and 12Servicio de Infectolog{\'i}a, Hospital de Pediatr{\'i}a {\textquoteleft}{\textquoteleft}J.P. Garrahan{\textquoteright}{\textquoteright}, Buenos Aires 1245, Argentina. 13School of Medical Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia. 14Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California 94107, USA. 15Department of Microbiology & Immunology and Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA. 16These authors contributed equally to this work. Correspondence should be addressed to S.K.A. ([email protected]) or M.J.D. ([email protected]). Copyright: Copyright 2009 Elsevier B.V., All rights reserved.",

year = "2007",

month = dec,

doi = "10.1038/ni1521",

language = "English (US)",

volume = "8",

pages = "1324--1336",

journal = "Nature Immunology",

issn = "1529-2908",

publisher = "Nature Publishing Group",

number = "12",

}

Dolan, MJ, Kulkarni, H, Camargo, JF, He, W, Smith, A, Anaya, JM, Miura, T, Hecht, FM, Mamtani, M, Pereyra, F, Marconi, V, Mangano, A, Sen, L, Bologna, R, Clark, RA, Anderson, SA, Delmar, J, O'Connell, RJ, Lloyd, A, Martin, J, Ahuja, SS, Agan, BK, Walker, BD, Deeks, SG & Ahuja, SK 2007, 'CCL3L1 and CCR5 influence cell-mediated immunity and affect HIV-AIDS pathogenesis via viral entry-independent mechanisms', Nature Immunology, vol. 8, no. 12, pp. 1324-1336. https://doi.org/10.1038/ni1521

TY - JOUR

T1 - CCL3L1 and CCR5 influence cell-mediated immunity and affect HIV-AIDS pathogenesis via viral entry-independent mechanisms

AU - Dolan, Matthew J.

AU - Kulkarni, Hemant

AU - Camargo, Jose F.

AU - He, Weijing

AU - Smith, Alison

AU - Anaya, Juan Manuel

AU - Miura, Toshiyuki

AU - Hecht, Frederick M.

AU - Mamtani, Manju

AU - Pereyra, Florencia

AU - Marconi, Vincent

AU - Mangano, Andrea

AU - Sen, Luisa

AU - Bologna, Rosa

AU - Clark, Robert A.

AU - Anderson, Stephanie A.

AU - Delmar, Judith

AU - O'Connell, Robert J.

AU - Lloyd, Andrew

AU - Martin, Jeffrey

AU - Ahuja, Seema S.

AU - Agan, Brian K.

AU - Walker, Bruce D.

AU - Deeks, Steven G.

AU - Ahuja, Sunil K.

N1 - Funding Information: 1Infectious Disease Clinical Research Program, 2Infectious Diseases Service and 3Henry M. Jackson Foundation, Wilford Hall United States Air Force Medical Center, Lackland Air Force Base, Texas 78236, USA. 4Veterans Administration Research Center for AIDS and HIV-1 Infection, South Texas Veterans Health Care System, and Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA. 5School of Psychology, University of Western Sydney, PenrithSth,NewSouthWales1797,Australia.6CellularBiologyandImmunogeneticsUnit,CorporaciónparaInvestigacionesBiologicas–UniversityofRosario,Cra7278-B-141, Medellin, Colombia. 7Partners AIDS Research Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. 8Division of AIDS, Harvard Medical School, Boston, Massachusetts 02114, USA. 9Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA. 10Department of Medicine, University of California, and San Francisco General Hospital, San Francisco, California 94110, USA. 11Laboratorio de Biología Celular y Retrovirus, and 12Servicio de Infectología, Hospital de Pediatría ‘‘J.P. Garrahan’’, Buenos Aires 1245, Argentina. 13School of Medical Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia. 14Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California 94107, USA. 15Department of Microbiology & Immunology and Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA. 16These authors contributed equally to this work. Correspondence should be addressed to S.K.A. ([email protected]) or M.J.D. ([email protected]). Copyright: Copyright 2009 Elsevier B.V., All rights reserved.

PY - 2007/12

Y1 - 2007/12

N2 - Although host defense against human immunodeficiency virus 1 (HIV-1) relies mainly on cell-mediated immunity (CMI), the determinants of CMI in humans are poorly understood. Here we demonstrate that variations in the genes encoding the chemokine CCL3L1 and HIV coreceptor CCR5 influence CMI in both healthy and HIV-infected individuals. CCL3L1-CCR5 genotypes associated with altered CMI in healthy subjects were similar to those that influence the risk of HIV transmission, viral burden and disease progression. However, CCL3L1-CCR5 genotypes also modify HIV clinical course independently of their effects on viral load and CMI. These results identify CCL3L1 and CCR5 as major determinants of CMI and demonstrate that these host factors influence HIV pathogenesis through their effects on both CMI and other viral entry-independent mechanisms.

AB - Although host defense against human immunodeficiency virus 1 (HIV-1) relies mainly on cell-mediated immunity (CMI), the determinants of CMI in humans are poorly understood. Here we demonstrate that variations in the genes encoding the chemokine CCL3L1 and HIV coreceptor CCR5 influence CMI in both healthy and HIV-infected individuals. CCL3L1-CCR5 genotypes associated with altered CMI in healthy subjects were similar to those that influence the risk of HIV transmission, viral burden and disease progression. However, CCL3L1-CCR5 genotypes also modify HIV clinical course independently of their effects on viral load and CMI. These results identify CCL3L1 and CCR5 as major determinants of CMI and demonstrate that these host factors influence HIV pathogenesis through their effects on both CMI and other viral entry-independent mechanisms.

UR - http://www.scopus.com/inward/record.url?scp=34548670468&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34548670468&partnerID=8YFLogxK

U2 - 10.1038/ni1521

DO - 10.1038/ni1521

M3 - Research Article

C2 - 17952079

AN - SCOPUS:34548670468

SN - 1529-2908

VL - 8

SP - 1324

EP - 1336

JO - Nature Immunology

JF - Nature Immunology

IS - 12

ER -

CCL3L1 and CCR5 influence cell-mediated immunity and affect HIV-AIDS pathogenesis via viral entry-independent mechanisms

Abstract

All Science Journal Classification (ASJC) codes

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this