The Open Virology Journal
2018, 12 : 1-13Published online 2018 February 28. DOI: 10.2174/1874357901812010001
Publisher ID: TOVJ-12-1
RESEARCH ARTICLE
Protection Efficacy of C5A Against Vaginal and Rectal HIV Challenges in Humanized Mice
2 Department of Pediatrics, University of Texas Medical Branch; Galveston, Texas
Department of Chemistry, Oak Crest Institute of Science; Monrovia, California
* Address correspondence to this author at the Department of Immunology & Microbiology, The Scripps Research Institute, Philippe A. Gallay , IMM-9, 10550 N. Torrey Pines Rd, La Jolla, USA; Tel: (858) 784-8180; E-mail: gallay@scripps.edu
ABSTRACT
Introduction:
In the absence of a vaccine, there is an urgent need for the identification of effective agents that prevent HIV transmission in uninfected individuals. Non-vaccine Biomedical Prevention (nBP) methods, such as topical or systemic pre-exposure prophylaxis (PrEP), are promising strategies to slow down the spread of AIDS.
Methods:
In this study, we investigated the microbicidal efficacy of the viral membrane-disrupting amphipathic SWLRDIWDWICEVLSDFK peptide called C5A. We chose the bone marrow/liver/thymus (BLT) humanized mouse model as vaginal and rectal HIV transmission models.
Results:
We found that the topical administration of C5A offers complete protection against vaginal and rectal HIV challenges in humanized mice. After demonstrating that C5A blocks genital HIV transmission in humanized mice, we examined the molecular requirements for its microbicidal property. We found that the removal of four amino acids on either end of C5A does not diminish its microbicidal efficacy. However, the removal of four amino acids at both the ends, abolishes its capacity to prevent vaginal or rectal HIV transmission, suggesting that the length of the peptide is a critical parameter for the microbicidal activity of C5A. Moreover, we demonstrated that the amphipathicity of the helical peptide as well as its hydrophobic surface represents key factors for the microbicidal activity of C5A in humanized mice.
Conclusion:
With its noncellular cytotoxic activity, its property of neutralizing both HSV and HIV, and its unique mechanism of action that disrupts the stability of the viral membrane, C5A represents an attractive multipurpose microbicidal candidate to be combined with other anti-HIV agents including antiretrovirals.