Michael Bolton

Publications (2)2.87 Total impact

• Article: Sequence similarity between the erythrocyte binding domain 1 of the Plasmodium vivax Duffy binding protein and the V3 loop of HIV-1 strain MN reveals binding residues for the Duffy Antigen Receptor for Chemokines

  Michael Bolton, Robert Garry
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  ABSTRACT: Abstract Background The surface glycoprotein (SU, gp120) of the human immunodeficiency virus (HIV) must bind to a chemokine receptor, CCR5 or CXCR4, to invade CD4+ cells. Plasmodium vivax uses the Duffy Binding Protein (DBP) to bind the Duffy Antigen Receptor for Chemokines (DARC) and invade reticulocytes. Results Variable loop 3 (V3) of HIV-1 SU and domain 1 of the Plasmodium vivax DBP share a sequence similarity. The site of amino acid sequence similarity was necessary, but not sufficient, for DARC binding and contained a consensus heparin binding site essential for DARC binding. Both HIV-1 and P. vivax can be blocked from binding to their chemokine receptors by the chemokine, RANTES and its analog AOP-RANTES. Site directed mutagenesis of the heparin binding motif in members of the DBP family, the P. knowlesi alpha, beta and gamma proteins abrogated their binding to erythrocytes. Positively charged residues within domain 1 are required for binding of P. vivax and P. knowlesi erythrocyte binding proteins. Conclusion A heparin binding site motif in members of the DBP family may form part of a conserved erythrocyte receptor binding pocket.
  Virology Journal. 01/2011;
• Article: Probiotics: potential to prevent HIV and sexually transmitted infections in women.

  Michael Bolton, Ariane van der Straten, Craig R Cohen
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  ABSTRACT: Women are at significant risk of human immunodeficiency virus (HIV) and sexually transmitted infection (STI) acquisition with the genital mucosa serving as the main portal of infection. Exogenously supplied lactobacillus used as a probiotic may prove a cost-effective, female-initiated method to prevent HIV and STI infection in women. A probiotic may act indirectly through treating and preventing recurrent bacterial vaginosis or directly by secreting endogenous (e.g., hydrogen peroxide) and exogenous substances that block HIV and STI transmission. This review summarizes the preclinical and clinical studies that have been conducted so far to test probiotic bacteria for these purposes. Although significant progress has been made in this field, more fundamental research is required to better understand vaginal ecology to maximize probiotic formulations. Once identified, a suitable product will require testing in a well-designed, randomized, placebo-controlled trial to measure its effectiveness in augmenting antibiotic treatment to prevent bacterial vaginosis. If results from such a trial demonstrate efficacy, future studies should be designed to determine whether a probiotic can significantly lower the risk for HIV and STIs in at-risk female populations.
  Sex Transm Dis 04/2008; 35(3):214-25. · 2.87 Impact Factor