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CCL3L1 copy number, HIV load, and immune reconstitution in sub-Saharan Africans

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posted on 12.03.2014, 16:38 by Eleni Aklillu, Linda Odenthal-Hesse, Jennifer Bowdrey, Abiy Habtewold, Eliford Ngaimisi, Getnet Yimer, Wondwossen Amogne, Sabina Mugusi, Omary Minzi, Eyasu Makonnen, Mohammed Janabi, Ferdinand Mugusi, Getachew Aderaye, Robert Hardwick, Beiyuan Fu, Maria Viskaduraki, Fengtang Yang, Edward J. Hollox
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.

Funding

This work was supported by a United Kingdom Medical Research Council New Investigator award [grant number GO801123] and a Wellcome Trust project grant [WT087663] to E.J.H.; European & Developing Countries Clinical Trials Partnership [grant numbers CT.2005.32030.001, CG_TA.05.40204_005]; and the Swedish International Development Cooperation Agency/Department for Research Cooperation [grant numbers HIV-2006-031, SWE 2007–270, VR 521-2011-3437]. Core facility funding was supported by the Wellcome Trust [grant number WT098051].

History

Citation

BMC Infectious Diseases, 2013, 13:536

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Biological Sciences/Department of Genetics

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VoR (Version of Record)

Published in

BMC Infectious Diseases

Publisher

BioMed Central

eissn

1471-2334

Copyright date

2013

Available date

12/03/2014

Publisher version

http://www.biomedcentral.com/1471-2334/13/536

Language

en

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