CCL3L1 copy number, HIV load, and immune reconstitution in sub-Saharan Africans.
BACKGROUND
The role of copy number variation of the CCL3L1 gene, encoding MIP1α, in contributing to the host variation in susceptibility and response to HIV infection is controversial. Here we analyse a sub-Saharan African cohort from Tanzania and Ethiopia, two countries with a high prevalence of HIV-1 and a high co-morbidity of HIV with tuberculosis.


METHODS
We use a form of quantitative PCR called the paralogue ratio test to determine CCL3L1 gene copy number in 1134 individuals and validate our copy number typing using array comparative genomic hybridisation and fiber-FISH.


RESULTS
We find no significant association of CCL3L1 gene copy number with HIV load in antiretroviral-naïve patients prior to initiation of combination highly active anti-retroviral therapy. However, we find a significant association of low CCL3L1 gene copy number with improved immune reconstitution following initiation of highly active anti-retroviral therapy (p = 0.012), replicating a previous study.


CONCLUSIONS
Our work supports a role for CCL3L1 copy number in immune reconstitution following antiretroviral therapy in HIV, and suggests that the MIP1α -CCR5 axis might be targeted to aid immune reconstitution.
Eleni
E
Aklillu
Linda
L
Odenthal-Hesse
Jennifer
J
Bowdrey
Abiy
A
Habtewold
Eliford
E
Ngaimisi
Getnet
G
Yimer
Wondwossen
W
Amogne
Sabina
S
Mugusi
Omary
O
Minzi
Eyasu
E
Makonnen
Mohammed
M
Janabi
Ferdinand
F
Mugusi
Getachew
G
Aderaye
Robert
R
Hardwick
Beiyuan
B
Fu
Maria
M
Viskaduraki
Fengtang
F
Yang
Department of Genetics, University of Leicester, University Road, Leicester, LE1 7RH, UK. Ejh33@le.ac.uk.
Edward J
EJ
Hollox
D000328:Adult; D019742:Chemokines, CC / Q000235:genetics*; D056915:DNA Copy Number Variations; D005002:Ethiopia / Q000453:epidemiology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D013636:Tanzania / Q000453:epidemiology; D019562:Viral Load
C492767:CCL3L1 protein, human; D019742:Chemokines, CC