title: Non-Cationic Proteins Are Associated with HIV Neutralizing Activity in Genital Secretions of Female Sex Workers.
abstract: OBJECTIVE
  Cationic proteins found in cervicovaginal secretions (CVS) are known to contribute to the early antiviral immune response against HIV-infection in vitro. We here aimed to define additional antiviral factors that are over-expressed in CVS from female sex workers at high risk of infection.
  
  
  METHODS
  CVS were collected from Kenyan HIV-seronegative (n = 34) and HIV-seropositive (n = 12) female sex workers, and were compared with those from HIV-seronegative low-risk women (n = 12). The highly exposed seronegative (HESN) sex workers were further divided into those with less (n = 22) or more (n = 12) than three years of documented sex work. Cationic protein-depleted CVS were assessed for HIV-neutralizing activity by a PBMC-based HIV-neutralizing assay, and then characterized by proteomics.
  
  
  RESULTS
  HIV neutralizing activity was detected in all unprocessed CVS, however only CVS from the female sex worker groups maintained its HIV neutralizing activity after cationic protein-depletion. Differentially abundant proteins were identified in the cationic protein-depleted secretions including 26, 42, and 11 in the HESN>3 yr, HESN<3 yr, and HIV-positive groups, respectively. Gene ontology placed these proteins into functional categories including proteolysis, oxidation-reduction, and epidermal development. The proteins identified in this study include proteins previously associated with the HESN phenotype in other cohorts as well as novel proteins not yet associated with anti-HIV activities.
  
  
  CONCLUSIONS
  While cationic proteins appear to contribute to the majority of the intrinsic HIV neutralizing activity in the CVS of low-risk women, a broader range of non-cationic proteins were associated with HIV neutralizing activity in HESN and HIV-positive female sex workers. These results indicate that novel protein factors found in CVS of women with high-risk sexual practices may have inherent antiviral activity, or are involved in other aspects of anti-HIV host defense, and warrant further exploration into their mode of action.
authors.affiliation: Proteomics Unit, National Laboratory for HIV Immunology, JC Wilt Infectious Disease Research Centre, Public Health Agency of Canada, Winnipeg, Manitoba, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Kenzie D M
authors.initials: KD
authors.lastname: Birse
authors.affiliation: Burnett School of Biomedical Sciences, University of Central Florida College of Medicine, Orlando, Florida, United States of America.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Cole
authors.affiliation: Unit of Infectious Diseases, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Taha
authors.initials: T
authors.lastname: Hirbod
authors.affiliation: Centre for the AIDS Programme of Research In South Africa, Doris Duke Medical Research Institute, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Congella, South Africa.
authors.forename: Lyle
authors.initials: L
authors.lastname: McKinnon
authors.affiliation: Proteomics Unit, National Laboratory for HIV Immunology, JC Wilt Infectious Disease Research Centre, Public Health Agency of Canada, Winnipeg, Manitoba, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada; Department of Medical Microbiology, Kenyatta National Hospital, University of Nairobi, Nairobi, Kenya.
authors.forename: Terry B
authors.initials: TB
authors.lastname: Ball
authors.affiliation: National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
authors.forename: Garrett R
authors.initials: GR
authors.lastname: Westmacott
authors.affiliation: Department of Medical Microbiology, Kenyatta National Hospital, University of Nairobi, Nairobi, Kenya.
authors.forename: Joshua
authors.initials: J
authors.lastname: Kimani
authors.affiliation: Proteomics Unit, National Laboratory for HIV Immunology, JC Wilt Infectious Disease Research Centre, Public Health Agency of Canada, Winnipeg, Manitoba, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada; National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada; Department of Medical Microbiology, Kenyatta National Hospital, University of Nairobi, Nairobi, Kenya.
authors.forename: Frank
authors.initials: F
authors.lastname: Plummer
authors.affiliation: Burnett School of Biomedical Sciences, University of Central Florida College of Medicine, Orlando, Florida, United States of America.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Cole
authors.affiliation: Proteomics Unit, National Laboratory for HIV Immunology, JC Wilt Infectious Disease Research Centre, Public Health Agency of Canada, Winnipeg, Manitoba, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada; Unit of Infectious Diseases, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Adam
authors.initials: A
authors.lastname: Burgener
authors.affiliation: Unit of Infectious Diseases, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Broliden
mesh_terms: D012634:Bodily Secretions / Q000276:immunology*; D004198:Disease Susceptibility; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007963:Leukocytes, Mononuclear / Q000821:virology; D065840:Protective Factors; D011506:Proteins / Q000378:metabolism*; D060386:Sex Workers; D014621:Vagina / Q000276:immunology / Q000378:metabolism* / Q000821:virology
chemical_list: D011506:Proteins