Innate Factors in Human Breast Milk Inhibit Cell-Free HIV-1 ... : JAIDS Journal of Acquired Immune Deficiency Syndromes (original) (raw)

Basic Science

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

Lyimo, Magdalena A MD; Howell, Alexandra L PhD; Balandya, Emmanuel MD; Eszterhas, Susan K PhD; Connor, Ruth I PhD

From the Departments of *Physiology and †Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH; and ‡VA Medical Center, White River Junction, VT.

Received for publication September 3, 2008; accepted March 2, 2009.

Supported by the National Institutes of Health AIDS International Training and Research Program/Fogarty International Center (FIC-2D43-TW006807) at Dartmouth Medical School.

Correspondence to: Ruth I. Connor, PhD, Department of Microbiology and Immunology, Dartmouth-Hitchcock Medical Center, HB 7556, Lebanon, NH 03756 (e-mail: [email protected]).

JAIDS Journal of Acquired Immune Deficiency Syndromes 51(2):p 117-124, June 2009. | DOI: 10.1097/QAI.0b013e3181a3908d

Abstract

Background:

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.

Objectives:

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.

Results:

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.

Conclusions:

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.