Contribution of variable CCL3L copy number to CCL3 protein production in two ethnically divergent South African populations

When accounting for the specific population, CCL3L copy number, a measure of the sum of chemokine- and non-chemokine-producing genes (CCL3La and CCL3Lb, respectively), has been reported to associate with risk of HIV-1 infection. In this study, we have described the distribution of CCL3La and CCL3Lb copy number variation in two populations, South African Africans (SAA) and South African Caucasians (SAC), and investigated the impact of these variations upon CCL3 protein production. Despite significant differences in CCL3La and CCL3Lb copy number, no differences in CCL3 production were noted between the two populations. Assuming equal contribution of CCL3 and each copy of CCL3La to CCL3 production, we found that SAC individuals produced higher levels of CCL3 per functional copy of CCL3La compared to SAA individuals (P<0.001). However, when individuals with comparable CCL3La and CCL3Lb gene copy numbers were compared, no difference in production per functional copy between SAA and SAC individuals was noted. Furthermore, we demonstrate that differences noted in cord blood mononuclear cell CCL3 production between HIV-1 intrapartum-infected (IP) and exposed uninfected (EU) infants with comparable CCL3L copy numbers could not be attributed to differences in CCL3Lb copy number. Collectively, our findings suggest that either the CCL3 gene may play a significant role in CCL3 production and/or that as yet undefined mechanisms regulate production of CCL3 from variable CCL3L copy number.