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PLoS One. 2014 Jul 18;9(7):e102395. doi: 10.1371/journal.pone.0102395. eCollection 2014.

Surfactant protein D inhibits HIV-1 infection of target cells via interference with gp120-CD4 interaction and modulates pro-inflammatory cytokine production.

Author information

1
Department of Innate Immunity, National Institute for Research in Reproductive Health (ICMR), Mumbai, Maharashtra, India.
2
Biomedical Informatics Centre, National Institute for Research in Reproductive Health (ICMR), Mumbai, Maharashtra, India.
3
Centre for Infection, Immunity and Disease Mechanisms, Brunel University, London, United Kingdom.
4
Department of Obstetrics and Gynecology, Seth G S Medical College and K E M Hospital, Mumbai, Maharashtra, India.
5
Department of Clinical Research, National Institute for Research in Reproductive Health (ICMR), Mumbai, Maharashtra, India.
6
Immunocompromised Host Research Section, Department of Infection and Immunity, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.

Abstract

Surfactant Protein SP-D, a member of the collectin family, is a pattern recognition protein, secreted by mucosal epithelial cells and has an important role in innate immunity against various pathogens. In this study, we confirm that native human SP-D and a recombinant fragment of human SP-D (rhSP-D) bind to gp120 of HIV-1 and significantly inhibit viral replication in vitro in a calcium and dose-dependent manner. We show, for the first time, that SP-D and rhSP-D act as potent inhibitors of HIV-1 entry in to target cells and block the interaction between CD4 and gp120 in a dose-dependent manner. The rhSP-D-mediated inhibition of viral replication was examined using three clinical isolates of HIV-1 and three target cells: Jurkat T cells, U937 monocytic cells and PBMCs. HIV-1 induced cytokine storm in the three target cells was significantly suppressed by rhSP-D. Phosphorylation of key kinases p38, Erk1/2 and AKT, which contribute to HIV-1 induced immune activation, was significantly reduced in vitro in the presence of rhSP-D. Notably, anti-HIV-1 activity of rhSP-D was retained in the presence of biological fluids such as cervico-vaginal lavage and seminal plasma. Our study illustrates the multi-faceted role of human SP-D against HIV-1 and potential of rhSP-D for immunotherapy to inhibit viral entry and immune activation in acute HIV infection.

PMID:
25036364
PMCID:
PMC4103819
DOI:
10.1371/journal.pone.0102395
[Indexed for MEDLINE]
Free PMC Article

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