title: β-defensin genomic copy number is associated with HIV load and immune reconstitution in sub-saharan Africans.
abstract: AIDS, caused by the retrovirus human immunodeficiency virus (HIV), is the leading cause of death of economically active people (age, 15-59 years) in sub-Saharan Africa. The host genetic variability of immune response to HIV and immune reconstitution following initiation of highly active antiretroviral therapy (HAART) is poorly understood. Here we focused on copy number variation of the β-defensin genes, which have been shown to have anti-HIV activity, and are important chemoattractants for Th17 lymphocytes via the chemokine receptor CCR6. We determined β-defensin gene copy number for 1002 Ethiopian and Tanzanian patients. We show that higher β-defensin copy number variation is associated with increased HIV load prior to HAART (P=.005) and poor immune reconstitution following initiation of HAART (P=.003). We suggest a model where variable amounts of β-defensin expression by mucosal cells, due to gene copy number variation, alters the efficacy of recruitment of Th17 lymphocytes to the site of infection, altering the dynamics of infection.
authors: Department of Genetics,  University of Leicester,  United Kingdom.
authors: Robert J
authors: RJ
authors: Hardwick
authors: Wondwossen
authors: W
authors: Amogne
authors: Sabina
authors: S
authors: Mugusi
authors: Getnet
authors: G
authors: Yimer
authors: Eliford
authors: E
authors: Ngaimisi
authors: Abiy
authors: A
authors: Habtewold
authors: Omary
authors: O
authors: Minzi
authors: Eyasu
authors: E
authors: Makonnen
authors: Mohammed
authors: M
authors: Janabi
authors: Lee R
authors: LR
authors: Machado
authors: Maria
authors: M
authors: Viskaduraki
authors: Ferdinand
authors: F
authors: Mugusi
authors: Getachew
authors: G
authors: Aderaye
authors: Lars
authors: L
authors: Lindquist
authors: Edward J
authors: EJ
authors: Hollox
authors: Eleni
authors: E
authors: Aklillu
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D060085:Coinfection; D005002:Ethiopia; D018628:Gene Dosage; D056726:Genetic Association Studies; D015894:Genome, Human; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000821:virology*; D006801:Humans; D016013:Likelihood Functions; D019713:Receptors, CCR5 / Q000235:genetics; D017384:Sequence Deletion; D013636:Tanzania; D014397:Tuberculosis, Pulmonary / Q000235:genetics / Q000276:immunology / Q000821:virology; D019562:Viral Load; D023083:beta-Defensins / Q000235:genetics*
chemical_list: D019380:Anti-HIV Agents; D019713:Receptors, CCR5; D023083:beta-Defensins