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.

1. Infectious Disease Clinical Research Program, Wilford Hall United States Air Force Medical Center, Lackland Air Force Base, Texas 78236, USA.
2. Infectious Diseases Service, Wilford Hall United States Air Force Medical Center, Lackland Air Force Base, Texas 78236, USA.
3. Henry M. Jackson Foundation, Wilford Hall United States Air Force Medical Center, Lackland Air Force Base, Texas 78236, USA.
4. Veterans 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.
5. School of Psychology, University of Western Sydney, Penrith Sth, New South Wales 1797, Australia.
6. Cellular Biology and Immunogenetics Unit, Corporación para Investigaciones Biologicas–University of Rosario, Cra 72 78-B-141, Medellin, Colombia.
7. Partners AIDS Research Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
8. Division of AIDS, Harvard Medical School, Boston, Massachusetts 02114, USA.
9. Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA.
10. Department of Medicine, University of California, and San Francisco General Hospital, San Francisco, California 94110, USA.
11. Laboratorio de Biología Celular y Retrovirus, Hospital de Pediatría "J.P. Garrahan", Buenos Aires 1245, Argentina.
12. Servicio de Infectología, Hospital de Pediatría "J.P. Garrahan", Buenos Aires 1245, Argentina.
13. School of Medical Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia.
14. Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California 94107, USA.
15. Department of Microbiology & Immunology and Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA.
16. These authors contributed equally to this work.

Correspondence to: Sunil K Ahuja^4,15 e-mail: ahujas@uthscsa.edu

Correspondence to: Matthew J Dolan^1,2,3,16 e-mail: mdolan@hjf.org

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.

NPG Journals

by Subject Area

• Chemistry

  • Chemistry
  • Drug discovery
  • Biotechnology
  • Materials
  • Methods & Protocols

• Clinical Practice & Research

  • Cancer
  • Cardiovascular medicine
  • Dentistry
  • Endocrinology
  • Gastroenterology & Hepatology
  • Methods & Protocols
  • Pathology & Pathobiology
  • Urology

• Earth & Environment

  • Earth sciences
  • Evolution & Ecology

• Life sciences

  • Biotechnology
  • Cancer
  • Development
  • Drug discovery
  • Evolution & Ecology
  • Genetics
  • Immunology
  • Medical research
  • Methods & Protocols
  • Microbiology
  • Molecular cell biology
  • Neuroscience
  • Pharmacology
  • Systems biology

• Physical sciences

  • Physics
  • Materials

by A - Z Index