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

撒哈拉以南非洲的 CCL3L1 拷贝数、HIV 载量和免疫重建

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作者: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.

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.

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.

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