Our previous study has shown that HIV-1 replicated at higher levels in neonatal (cord) blood monocytes/macrophages and T-lymphocytes compared with adult blood cells. However, it is not known whether this differential HIV-1 replication also occurs in naive and/or memory T-lymphocytes. We, therefore, compared HIV-1 replication in CD3+ and CD4+ naive (CD45RA(+)) and memory (CD45RO(+))T-lymphocytes isolated from five cord and adult blood donors. We found that HIV-1 replicated at higher levels in both CD3+ and CD4+ CD45RA+ and CD45RO(+) T-Iymphocytes isolated from cord blood compared with adult blood. In addition, there was no difference in the cell surface expression of CD4. CXCR4 and CCR5 on cord blood CD45RA+ and CD45RO(+) T-lymphocytes compared with adult blood cells. Furthermore, we found that there was an increase in HIV-1 gene expression in cord blood CD45RA(+) and CD45RO(+) T-lymphocytes compared with adult blood cells by using a single-cycle replication competent HIV-1-NL4-3-Env(-)R(+) luciferase amphotropic virus, which measures HIV-1 transcriptional activity independent of CD4 and CXCR4 or CCR5 expression. In summary, HIV-1 replicated at higher levels in cord blood CD45RA(+) and CD45RO(+) T-lymphocytes compared with adult blood cells and this differential replication is influenced at the level of HIV-1 gene expression. (C) 2011 Elsevier Inc. All rights reserved.