B-defensin genomic copy number is associated with HIV load and immune reconstitution in sub-Saharan Africans

Robert J Hardwick, Wondwossen Amogne, Sabina Mugusi, Getnet Yimer, Eliford Ngaimisi, Abiy Habtewold, Omary Minzi, Eyasu Makonnen, Mohammed Janabi, Lee Machado, Maria Viskaduraki, Ferdinand Mugusi, Getachew Aderaye, Lars Lindquist, Edward J Hollox, Eleni Aklillu

Research output: Contribution to journalArticleResearch

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.
Original languageEnglish
JournalThe Journal of Infectious Diseases
Volume206
Issue number7
Early online date26 Jul 2012
DOIs
Publication statusPublished - 1 Oct 2012

Fingerprint

Defensins
Highly Active Antiretroviral Therapy
HIV
Gene Dosage
Lymphocytes
Africa South of the Sahara
Chemokine Receptors
Chemotactic Factors
Retroviridae
Infection
Cause of Death
Acquired Immunodeficiency Syndrome
Genes

Cite this

Hardwick, Robert J ; Amogne, Wondwossen ; Mugusi, Sabina ; Yimer, Getnet ; Ngaimisi, Eliford ; Habtewold, Abiy ; Minzi, Omary ; Makonnen, Eyasu ; Janabi, Mohammed ; Machado, Lee ; Viskaduraki, Maria ; Mugusi, Ferdinand ; Aderaye, Getachew ; Lindquist, Lars ; Hollox, Edward J ; Aklillu, Eleni. / B-defensin genomic copy number is associated with HIV load and immune reconstitution in sub-Saharan Africans. In: The Journal of Infectious Diseases. 2012 ; Vol. 206, No. 7.
@article{0f5a2f04d51e4bb5bc2ee5dd28148cb6,
title = "B-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.",
author = "Hardwick, {Robert J} and Wondwossen Amogne and Sabina Mugusi and Getnet Yimer and Eliford Ngaimisi and Abiy Habtewold and Omary Minzi and Eyasu Makonnen and Mohammed Janabi and Lee Machado and Maria Viskaduraki and Ferdinand Mugusi and Getachew Aderaye and Lars Lindquist and Hollox, {Edward J} and Eleni Aklillu",
year = "2012",
month = "10",
day = "1",
doi = "10.1093/infdis/jis448",
language = "English",
volume = "206",
journal = "The Journal of Infectious Diseases",
issn = "1537-6613",
publisher = "Oxford University Press",
number = "7",

}

Hardwick, RJ, Amogne, W, Mugusi, S, Yimer, G, Ngaimisi, E, Habtewold, A, Minzi, O, Makonnen, E, Janabi, M, Machado, L, Viskaduraki, M, Mugusi, F, Aderaye, G, Lindquist, L, Hollox, EJ & Aklillu, E 2012, 'B-defensin genomic copy number is associated with HIV load and immune reconstitution in sub-Saharan Africans', The Journal of Infectious Diseases, vol. 206, no. 7. https://doi.org/10.1093/infdis/jis448

B-defensin genomic copy number is associated with HIV load and immune reconstitution in sub-Saharan Africans. / Hardwick, Robert J; Amogne, Wondwossen; Mugusi, Sabina; Yimer, Getnet; Ngaimisi, Eliford; Habtewold, Abiy; Minzi, Omary; Makonnen, Eyasu; Janabi, Mohammed; Machado, Lee; Viskaduraki, Maria; Mugusi, Ferdinand; Aderaye, Getachew; Lindquist, Lars; Hollox, Edward J; Aklillu, Eleni.

In: The Journal of Infectious Diseases, Vol. 206, No. 7, 01.10.2012.

Research output: Contribution to journalArticleResearch

TY - JOUR

T1 - B-defensin genomic copy number is associated with HIV load and immune reconstitution in sub-Saharan Africans

AU - Hardwick, Robert J

AU - Amogne, Wondwossen

AU - Mugusi, Sabina

AU - Yimer, Getnet

AU - Ngaimisi, Eliford

AU - Habtewold, Abiy

AU - Minzi, Omary

AU - Makonnen, Eyasu

AU - Janabi, Mohammed

AU - Machado, Lee

AU - Viskaduraki, Maria

AU - Mugusi, Ferdinand

AU - Aderaye, Getachew

AU - Lindquist, Lars

AU - Hollox, Edward J

AU - Aklillu, Eleni

PY - 2012/10/1

Y1 - 2012/10/1

N2 - 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.

AB - 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.

U2 - 10.1093/infdis/jis448

DO - 10.1093/infdis/jis448

M3 - Article

VL - 206

JO - The Journal of Infectious Diseases

JF - The Journal of Infectious Diseases

SN - 1537-6613

IS - 7

ER -