Innate Factors in Human Breast Milk Inhibit Cell-Free HIV-1 but Not Cell-Associated HIV-1 Infection of CD4+ Cells

Abstract

Transmission of HIV from mother to child through breast-feeding remains a global health challenge, particularly in developing countries. Breast milk from an HIV-infected women may contain both cell-free HIV-1 and cell-associated virus; however, the impact of human breast milk on HIV infection and replication in CD4 cells remain poorly understood. In the present study, we evaluated the effects of breast milk in vitro on infection of CD4 cells with cell-free HIV-1, including effects on HIV-1 receptor expression, reverse transcription, integration, and viral transcription. Additionally, we evaluated the ability of breast milk to inhibit cell-associated transmission of HIV-1 from infected CD4 T lymphocytes. Our results demonstrate that breast milk potently inhibits infection with cell-free HIV-1 in vitro independently of viral tropism and significantly decreases HIV-1 reverse transcription and integration in CD4 cells. However, the inhibitory effect of breast milk on HIV-1 infection of CD4 cells was lost during extended culture, and direct coculture of HIV-infected CD4 T lymphocytes with susceptible target cells revealed that breast milk was ineffective at blocking cell-associated HIV-1 infection. Our findings suggest that breast milk may provide a protective function against cell-free HIV-1 but may be less effective at blocking infection by cell-associated virus.