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

Matthew J. Dolan, Hemant Kulkarni, Jose Camargo Galvis, 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

Research output: Contribution to journalArticle

138 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1324-1336
Number of pages13
JournalNature Immunology
Volume8
Issue number12
DOIs
StatePublished - Dec 2007
Externally publishedYes

Fingerprint

Cellular Immunity
Acquired Immunodeficiency Syndrome
HIV
Viral Load
Genotype
Chemokine CCL3
Virus Diseases
Disease Progression
HIV-1
Healthy Volunteers
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

CCL3L1 and CCR5 influence cell-mediated immunity and affect HIV-AIDS pathogenesis via viral entry-independent mechanisms. / Dolan, Matthew J.; Kulkarni, Hemant; Camargo Galvis, Jose; He, Weijing; Smith, Alison; Anaya, Juan Manuel; Miura, Toshiyuki; Hecht, Frederick M.; Mamtani, Manju; Pereyra, Florencia; Marconi, Vincent; Mangano, Andrea; Sen, Luisa; Bologna, Rosa; Clark, Robert A.; Anderson, Stephanie A.; Delmar, Judith; O'Connell, Robert J.; Lloyd, Andrew; Martin, Jeffrey; Ahuja, Seema S.; Agan, Brian K.; Walker, Bruce D.; Deeks, Steven G.; Ahuja, Sunil K.

In: Nature Immunology, Vol. 8, No. 12, 12.2007, p. 1324-1336.

Research output: Contribution to journalArticle

Dolan, MJ, Kulkarni, H, Camargo Galvis, J, 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
Dolan, Matthew J. ; Kulkarni, Hemant ; Camargo Galvis, Jose ; He, Weijing ; Smith, Alison ; Anaya, Juan Manuel ; Miura, Toshiyuki ; Hecht, Frederick M. ; Mamtani, Manju ; Pereyra, Florencia ; Marconi, Vincent ; Mangano, Andrea ; Sen, Luisa ; Bologna, Rosa ; Clark, Robert A. ; Anderson, Stephanie A. ; Delmar, Judith ; O'Connell, Robert J. ; Lloyd, Andrew ; Martin, Jeffrey ; Ahuja, Seema S. ; Agan, Brian K. ; Walker, Bruce D. ; Deeks, Steven G. ; Ahuja, Sunil K. / CCL3L1 and CCR5 influence cell-mediated immunity and affect HIV-AIDS pathogenesis via viral entry-independent mechanisms. In: Nature Immunology. 2007 ; Vol. 8, No. 12. pp. 1324-1336.
@article{ad5aed84de2447218c35d1bacf3aaf31,
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 Galvis}, Jose 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.}",
year = "2007",
month = "12",
doi = "10.1038/ni1521",
language = "English (US)",
volume = "8",
pages = "1324--1336",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "12",

}

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 Galvis, Jose

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.

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 - Article

C2 - 17952079

AN - SCOPUS:34548670468

VL - 8

SP - 1324

EP - 1336

JO - Nature Immunology

JF - Nature Immunology

SN - 1529-2908

IS - 12

ER -