| Introduction: Under normal conditions, the obligatory co-receptor for early HIV-1 entry, i.e. the chemokine receptor CCR5, is not expressed on naive CD4+ T cells which are the predominant if not only T cell population in the neonate. However, neonates can become infected with R5 HIV-1 through maternal-to-child-transmission (MTCT). HIV-1 infection in neonates also progresses more rapidly than in adults with higher plasma viral loads (>106 copies per ml), and an increased risk on treatment failure of HAART. Thus, although low numbers of CCR5+ T cells are present, rapid infection and replication of HIV-1 does occur in newly infected neonates and infants. Hypothesis: HIV-1 infection in neonates targets CCR5+ monocytes which in this phase of life may have high proliferative potential. Alternatively, HIV-1 infected neonates have a unique naïve CD4+ T cell population that expresses CCR5 or another yet unidentified coreceptor and that is proliferating due to stimulation by cognate antigen or growth factors, thereby maintaining a naive phenotype. Objective: To elucidate the HIV-1 target cell in neonates and the cellular and viral components involved in early HIV-1 infection of monocytes and naïve CD4+ T lymphocytes in infants. |
