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Clinical and Vaccine Immunology, October 2006, p. 1111-1118, Vol. 13, No. 10
1071-412X/06/$08.00+0     doi:10.1128/CDLI.00426-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Comparison of Human Immunodeficiency Virus Type 1-Specific Inhibitory Activities in Saliva and Other Human Mucosal Fluids{triangledown}

Shamim H. Kazmi,1,{dagger} Julian R. Naglik,1 Simon P. Sweet,1 Robert W. Evans,2 Siobhan O'Shea,3 Jangu E. Banatvala,3 and Stephen J. Challacombe1*

Oral AIDS Research Unit, Department of Oral Medicine and Immunology, King's College London Dental Institute at Guy's, King's College, and St. Thomas' Hospitals, King's College London, London, United Kingdom,1 Division of Biomolecular Sciences, Guy's Campus, King's College London, London, United Kingdom,2 Department of Virology, St. Thomas's Hospital, King's College London, London, United Kingdom3

Received 2 December 2005/ Returned for modification 14 February 2006/ Accepted 12 August 2006

Several human mucosal fluids are known to possess an innate ability to inhibit human immunodeficiency virus type 1 (HIV-1) infection and replication in vitro. This study compared the HIV-1 inhibitory activities of several mucosal fluids, whole, submandibular/sublingual (sm/sl), and parotid saliva, breast milk, colostrum, seminal plasma, and cervicovaginal secretions, from HIV-1-seronegative donors by using a 3-day microtiter infection assay. A wide range of HIV-1 inhibitory activity was exhibited in all mucosal fluids tested, with some donors exhibiting high levels of activity while others showed significantly lower levels. Colostrum, whole milk, and whole saliva possessed the highest levels of anti-HIV-1 activity, seminal fluid, cervicovaginal secretions, and sm/sl exhibited moderate levels, and parotid saliva consistently demonstrated the lowest levels of HIV-1 inhibition. Fast protein liquid chromatography gel filtration studies revealed the presence of at least three distinct peaks of inhibitory activity against HIV-1 in saliva and breast milk. Incubation of unfractionated and fractionated whole saliva with antibodies raised against human lactoferrin (hLf), secretory leukocyte protease inhibitor (SLPI), and, to a lesser extent, MG2 (high-molecular-weight mucinous glycoprotein) reduced the HIV-1 inhibitory activity significantly. The results suggest that hLf and SLPI are two key components responsible for HIV-1 inhibitory activity in different mucosal secretions. The variation in HIV inhibitory activity between the fluids and between individuals suggests that there may be major differences in susceptibility to HIV infection depending both on the individual and on the mucosal fluid involved.

* Corresponding author. Mailing address: Department of Oral Medicine, Pathology and Immunology, King's College London Dental Institute at Guy's, King's College, and St. Thomas' Hospitals, Floor 28, Guy's Tower, King's College London, London SE1 9RT, United Kingdom. Phone: 020 7188 4374. Fax: 020 7188 4375. E-mail: stephen.challacombe{at}kcl.ac.uk.

{triangledown} Published ahead of print on 23 August 2006.

{dagger} Present address: Jefferiss Trust Research Laboratories, Wright-Fleming Institute, St. Mary's Campus, Imperial College London, London, United Kingdom.

Clinical and Vaccine Immunology, October 2006, p. 1111-1118, Vol. 13, No. 10
1071-412X/06/$08.00+0     doi:10.1128/CDLI.00426-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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