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

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 he...

Full description

Autores:
Tipo de recurso:
Fecha de publicación:
2007
Institución:
Universidad del Rosario
Repositorio:
Repositorio EdocUR - U. Rosario
Idioma:
eng
OAI Identifier:
oai:repository.urosario.edu.co:10336/22641
Acceso en línea:
https://doi.org/10.1038/ni1521
https://repository.urosario.edu.co/handle/10336/22641
Palabra clave:
Chemokine receptor CCR5
Macrophage inflammatory protein 1alpha
Macrophage inflammatory protein 1alpha L1
Unclassified drug
Acquired immune deficiency syndrome
Animal experiment
Animal model
Article
Cellular immunity
Controlled study
Disease course
DNA modification
Genetic association
Genetic variability
Genotype
Host resistance
Human
Human immunodeficiency virus 1
Human immunodeficiency virus infection
Infection risk
Mouse
Nonhuman
Pathogenesis
Priority journal
Virus load
Virus transmission
Virus virulence
Acquired Immunodeficiency Syndrome
Genotype
HIV Infections
HIV-1
Humans
Viral Load
Cellular
CC
CCR5
Chemokines
Immunity
Receptors
Rights
License
Abierto (Texto Completo)
Description
Summary: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.